Si può desiderare di provare un trattamento naturale disfunzione erettile come un diverso per i problemi di costruzione. Al giorno d oggi ci sono diverse terapie sul mercato, ma un trattamento naturale disfunzione erettile è stato confermato qualche ora e ora di nuovo per dare risultati efficienti e permanenti. Cos è la disfunzione sessuale? L incapacità di sviluppare o sostenere una costruzione abbastanza lungo per fare l amore è chiamato disfunzione erettile, ED https://farmacia-senzaricetta.it/ o (maschio) problemi di erezione. Tutti gli uomini possono avere problemi di costruzione di volta in volta e gli scienziati considerano ED essere presenti se si verificano problemi di costruzione almeno il 25% del tempo. Alcuni fatti duri: ED Può essere dovuto a problemi emotivi. Stress, pressione, giltiness, depressione, bassa autostima e ansia prestazioni può essere la causa dei vostri problemi di costruzione. La ricerca ha confermato che il 90 per cento della disfunzione erettile è fisica in origine, non emotiva. L impotenza colpisce la maggior parte degli uomini durante la loro vita e può essere dovuto a troppo colesterolo, problemi cardiaci, diabete, ipertensione, fumo o alcol. Alcuni rimedi possono essere la ragione. Le questioni legate al movimento sono collegate. Se ti occupi dei tuoi problemi di movimento, hai piu possibilita di risolvere questo problema. Qui ci sono 5 consigli facili su come aumentare la circolazione: 1. Mangia i pasti giusti. Questo ti rendera il flusso sanguigno ovvio. Una grande parte di rimanere sani e anche mantenere il flusso sanguigno ovvio è legato al vostro piano di alimentazione quotidiana e quello che si mangia. Una buona cura per la disfunzione erettile è mangiare un piano a basso contenuto di grassi e grande alimentazione di fibre. Mangiare fibre tutti i giorni e questo viene scoperto in prodotti cerealicoli cereali integrali, frutta e verdura. Evitare il più possibile pasti pronti o pasti non sani. 2. Wonder herbal rimedi. Molti rimedi vegetali per ED eseguire bene come possono migliorare il movimento. Hanno molto meno reazioni avverse rispetto ai farmaci convenzionali e si svolgono in modo efficiente per migliorare hardons e la forza, troppo. Erbe naturali come Ginkgo Biloba sono utilizzati come una strategia per ED. Gli specialisti di erboristeria credono anche che le spezie o le erbe come noce moscata, portano al movimento intorno al corpo, tra cui il pene. 3. Vitamine naturali vitali. Gli scienziati sanitari hanno scoperto che una mancanza di supplemento è tipico tra gli uomini con ED in particolare vitamina A. Se si ha una mancanza del nutriente ossido di zinco, Questo è stato confermato per portare alla disfunzione erettile. Queste inadeguatezze derivano dal fatto che molti valori nutrizionali in quello che mangiamo piano non sono sufficienti. Aggiungere al vostro fabbisogno di nutrienti aumenterà la circolazione del sistema e migliorare questa condizione. Gli integratori alimentari sono completamente naturali, quindi non dovrete preoccuparvi dei rischi di reazioni avverse. Inoltre, queste vitamine naturali sono utili per il vostro benessere over-all. Oltre a questi vantaggi benessere, disfunzione erettile vitamine naturali e integratori costano molto meno di farmaci rimedi. 4. Esercitare. Fai una mossa e non un tablet vibrante. Camminare farà di più per migliorare e sostenere hardons di qualsiasi altra compressa chimica nel lungo periodo. Il fitness fisico manterrà bassi livelli di pressione e mantenere grandi stadi di movimento. Andando per un 20-30 minuti di movimento rapido ogni giorno, può affrontare questo problema e può sostenere la vostra libido senza l uso di qualsiasi farmaco. 5. Sottolineare. Questo è il peggior attaccante per problemi di erezione. Scopri diversi metodi per riposare. Alcuni metodi tipici per riposare includono la lettura di un libro, la meditazione, un bagno rilassante o allenamenti di respirazione. Sto solo imparando alcuni semplici allenamenti di respirazione che possono migliorare significativamente il movimento nel reparto pantaloni. Una naturale disfunzione erettile soluzioni di trattamento stanno diventando sempre più popolare con gli uomini. Questi rimedi a base di erbe sono preferiti perché non hanno reazioni avverse e sono confermati essere efficiente come il farmaco. La maggior parte degli uomini combattere parlano dei loro problemi, in particolare la disfunzione erettile come c è poca discussione sui problemi di erezione. La verita e che ED ha un impatto su piu di dieci milioni di uomini solo negli Stati Uniti. Non siete soli e l aiuto è disponibile.
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Curcumin, the Golden Spice From Indian Saffron, Is a Chemosensitizer andRadiosensitizer for Tumors and Chemoprotector and Radioprotector forNormal Organs
Ajay Goela; Bharat B. Aggarwalba Gastrointestinal Cancer Research Laboratory, Department of Internal Medicine, Charles A. SammonsCancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA bCytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
To cite this Article Goel, Ajay and Aggarwal, Bharat B.(2010) 'Curcumin, the Golden Spice From Indian Saffron, Is a
Chemosensitizer and Radiosensitizer for Tumors and Chemoprotector and Radioprotector for Normal Organs', Nutrition
and Cancer, 62: 7, 919 — 930To link to this Article: DOI: 10.1080/01635581.2010.509835URL:
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The publisher does not give any warranty express or implied or make any representation that the contentswill be complete or accurate or up to date. The accuracy of any instructions, formulae and drug dosesshould be independently verified with primary sources. The publisher shall not be liable for any loss,actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directlyor indirectly in connection with or arising out of the use of this material. Nutrition and Cancer, 62(7), 919–930Copyright C 2010, Taylor & Francis Group, LLCISSN: 0163-5581 print / 1532-7914 onlineDOI: 10.1080/01635581.2010.509835
Curcumin, the Golden Spice From Indian Saffron, Is a Chemosensitizer and Radiosensitizer for Tumors and Chemoprotector and Radioprotector for Normal Organs Ajay Goel Gastrointestinal Cancer Research Laboratory, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA Bharat B. Aggarwal Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA directly quench free radicals, and inhibit p300 HAT activity. These Curcumin (diferuloylmethane), the yellow pigment in Indian preclinical studies are expected to lead to clinical trials to prove the saffron (Curcuma longa; also called turmeric, haldi, or haridara in potential of this age-old golden spice for treating cancer patients. the East and curry powder in the West), has been consumed by peo- ple for centuries as a dietary component and for a variety of proin- flammatory ailments. Extensive research within the last decade in cell culture and in rodents has revealed that curcumin can sensi- INTRODUCTION tize tumors to different chemotherapeutic agents including doxoru- bicin, 5-FU, paclitaxel, vincristine, melphalan, butyrate, cisplatin,
heptadiene-3,5-dione), a polyphenol, is a natural compound
celecoxib, vinorelbine, gemcitabine, oxaliplatin, etoposide, sulfino-
that is derived from turmeric, the powdered rhizome of the
sine, thalidomide, and bortezomib. Chemosensitization has been observed in cancers of the breast, colon, pancreas, gastric, liver,
medicinal plant Curcuma longa Linn (also known as turmeric). blood, lung, prostate, bladder, cervix, ovary, head and neck, and
The yellow-pigmented fraction of turmeric primarily consists
brain and in multiple myeloma, leukemia, and lymphoma. Similar
of various curcuminoids including curcumin I (or curcumin,
studies have also revealed that this agent can sensitize a variety of
≈77%), curcumin II (demethoxycurcumin, ≈17%) and cur-
tumors to gamma radiation including glioma, neuroblastoma, cer-
cumin III (bisdemethoxycurcumin, ≈3%). The curcuminoid
vical carcinoma, epidermal carcinoma, prostate cancer, and colon cancer. How curcumin acts as a chemosensitizer and radiosensi-
complex, collectively, is frequently referred to as Indian saffron,
tizer has also been studied extensively. For example, it downreg-
yellow ginger, yellow root, and haldi. Curcumin has been used
ulates various growth regulatory pathways and specific genetic
for centuries throughout Asia as a food additive, cosmetic, and
targets including genes for NF-κB, STAT3, COX2, Akt, antiapop-
as a traditional herbal medicine. As a spice, it provides curry
totic proteins, growth factor receptors, and multidrug-resistance
with its distinctive color and flavor. Furthermore, traditional
proteins. Although it acts as a chemosensitizer and radiosensitizer for tumors in some cases, curcumin has also been shown to pro-
Indian medicine has considered curcumin a drug effective for
tect normal organs such as liver, kidney, oral mucosa, and heart
various respiratory conditions (asthma, bronchial hyperactivity,
from chemotherapy and radiotherapy-induced toxicity. The pro-
and allergy) as well as for other disorders including anorexia,
tective effects of curcumin appear to be mediated through its abil-
coryza, cough, hepatic diseases, and sinusitis (1,2). Over the
ity to induce the activation of NRF2 and induce the expression of
past decade, several studies have substantiated the potential
antioxidant enzymes (e.g., hemeoxygenase-1, glutathione peroxi- dase, modulatory subunit of gamma-glutamyl-cysteine ligase, and
prophylactic or therapeutic value of curcumin and have
NAD(P)H:quinone oxidoreductase 1, increase glutathione (a prod-
unequivocally supported reports of its anti-inflammatory (3,4),
uct of the modulatory subunit of gamma-glutamyl-cysteine ligase),
antioxidant (5), anticarcinogenic (6–8), hepatoprotective (9),thrombosuppressive (10), cardioprotective (11), antiarthritic(12), and anti-infectious (13) properties. One of the most com-
Submitted 27 February 2010; accepted in final form 16 July 2010.
pelling reasons for continued interest in exploring the cancer
Address correspondence to Bharat B. Aggarwal, Cytokine Research
chemopreventive and therapeutic uses of curcumin has been
Laboratory, Department of Experimental Therapeutics, and Depart-
curcumin’s ability to influence a diverse range of molecular tar-
ment of Radiation Oncology, The University of Texas, M. D. AndersonCancer Center, Houston, TX 77030. Phone: 713-792-3503. Fax: 713-
gets within cells. To date, no studies have reported any toxicity
794-1613. E-mail: [email protected]
associated with the use of curcumin in either animals or humans.
Undisputed scientific evidence suggests that curcumin sup-
frequent cause of cancer-related deaths in these patients. There-
presses all 3 stages of carcinogenesis: initiation, promotion,
fore, understanding the molecular basis of MDR and developing
and progression. Several genetic targets may mediate cancer-
drugs and treatment regimens to prevent tumor resistance is an
related efficacy of curcumin, but inhibition of nuclear factor
kappa B (NF-κB) and subsequent downregulation of various
Drug resistance and toxicity can also be dictated by several
NF-κB-related proinflammatory pathways are very likely the
factors including metabolism and excretion of the drug, inade-
primary features accounting for its efficacy (14). Curcumin has
quate or poor access of the drug to the tumor, and the role of
been studied for its chemopreventive potential in a wide variety
various drug metabolizing enzymes such as cytochrome P450s,
of cancers, in both preclinical studies and in clinical trials (re-
which are often overexpressed (24). In recent years, a new con-
viewed in Goel et al. (15)). However, recent data indicate that
cept has been proposed that suggests that another important
in addition to its chemopreventive role, curcumin has tremen-
reason why cancer therapies might fail and tumors develop re-
dous potential as a chemosensitizer and radiosensitizer as well
lapse is because these strategies do not target rare tumor cells or
as chemoprotector and radioprotector. This is of great interest
so-called cancer stem cells. According to this hypothesis, which
given the plethora of diverse molecular targets curcumin can
is still in its nascent stages, a small fraction of tumor cells has
regulate. The fact that curcumin can achieve all of these effects
the unlimited capacity to self-renew, have extensive unlimited
without any toxicity makes developing curcumin as an adjunct
slow proliferation potential, and can give rise to phenotypically
to standard chemotherapy and radiotherapy an important goal.
diverse progeny of cancer cells with variable proliferative ca-
It may offer a therapeutic advantage in the clinical management
pacity (25,26). It is believed that these cancer stem cells are
of various refractory tumors over other, standard modalities.
often resistant to chemotherapy and radiation, and treatments
Constant challenges in cancer chemotherapy and radiother-
that substantially reduce tumor mass by removing proliferating
apy are the adverse toxicity and resistance associated with these
tumor cells often fail to target these stem cells and cure patients
treatment regimens. Among these are hair loss, diarrhea, fatigue,
completely with certain cancers. According to this viewpoint,
mouth sores, and low blood counts. Many patients experience
these cancer stem cells are immune to any therapies, maintain
chemotherapy-induced toxicity because these drugs are heavily
their “stemness,” and continue to repopulate tumor mass with
protein bound and can damage normal cells and tissues in many
a continuous supply of new cancer cells (27). This new under-
ways. As much as we understand now that tumor initiation and
standing has promoted researchers and pharmaceutical compa-
development is a multistep process involving a series of ge-
nies to shift their efforts to develop targeted or more effective
netic and epigenetic events, why most therapeutic approaches
anticancer therapies that could either induce differentiation of
become increasingly ineffective over the course of treatment
cancer stem cells to lose their stemness or completely eliminate
remains poorly understood. Regardless, cancer cells become re-
sistant to chemotherapeutic drugs through mechanisms that may
In this context, curcumin seems to offer an ideal agent be-
involve mutation or overexpression of the drug’s specific target,
cause over the last two decades, significant evidence has indi-
drug inactivation, or efflux of the drug out of the cell (16).
cated anticancer potential of curcumin. In fact, it is very encour-
Historically, chemotherapeutic strategies have used a variety
aging to notice that unlike many “targeted” chemotherapeutic
of single drugs or drug combinations that interfere with cellular
drugs that suffer from toxicity and resistance concerns, curcumin
machinery in order to achieve the desired effect. Knowledge
by itself can target several of these molecular targets/pathways
gained from these studies and improved understanding of the
without any associated toxicity or resistance. In fact, newer data
molecular alterations that are present within tumor cells have
suggest that in addition to its chemopreventive ability, curcumin
paved the way for the development of targeted therapies. Inter-
can sensitize many human cancers to chemotherapy and radi-
estingly, resistance appears to occur not only with traditional
ation, as well as afford protection against the toxicity of these
chemotherapy but also to targeted chemotherapies such as her-
treatment regimens. This review summarizes the potential role
ceptin, which targets human epidermal growth factor receptor 2
of curcumin as both a chemosensitizer and radiosensitizer as
(HER-2) in breast cancer (17); tamoxifen, which targets estro-
well as its ability to function as a chemoprotector and radiopro-
gen receptor (ER) in breast cancer (18); remicade or infliximab,
tector in different forms of tumors.
which targets tumor necrosis factor (TNFα) in multiple inflam-matory diseases (19,20); gleevac, targeted against the kinase ac-tivity of BCR-ABL gene in chronic myelogenous leukemia (21);
CURCUMIN AS A CHEMOSENSITIZER
and erbitux or gefitinib, which inhibits epidermal growth fac-
Curcumin not only acts as a cancer preventive, but data sug-
tor receptor (EGFR) kinase (22). In some instances, it becomes
gest that curcumin treatment may be able to eliminate chemore-
even more complex when tumors in some patients recur after
sistant cancers by sensitizing these tumors to chemotherapy and
therapy and show resistance to multiple drugs, a phenomenon
radiation by increasing the rate of apoptosis. In this section,
often referred to as multidrug resistance (MDR) (23). MDR
we summarize the current state of the biomedical literature on
tumors are not only resistant to many combinations of can-
curcumin as a chemosensitizer. Data from both in vitro and
cer chemotherapy, but they also tend to metastasize and are a
in vivo studies have supported the potential chemosensitizing
Curcumin potentiates the effect of chemotherapya
Potentiates cytotoxic effects of doxorubicin, 5-FU, and paclitaxel against prostate cancer cells
Sensitizes multiple myeloma cells to vincristine and melphalan
Enhances cytotoxicity of cisplatin against ovarian cancer cells in culture
Potentiates antitumor effects of sodium butyrate against erythroleukemic cells
Potentiates growth inhibition effects of 5-FU against human gastric carcinoma cells in culture
Exhibits both additive and sub-additive antitumor and apoptotic effects of doxorubicin against liver
Potentiates the antitumor and apoptotic effects of cisplatin against hepatocellular carcinoma cells
Enhances antitumor effects of taxol against cervical cancer cells in culture
Potentiates the cytotoxicity of paclitaxel toward breast cancer cells in culture
Potentiates apoptotic effects of celecoxib against human pancreatic cancer cells
Synergistic effects with celecoxib in growth inhibition in colon cancer cells
Enhances apoptotic effects of cisplatin against cervical cancer SiHa cells, but not HeLa cells
Enhances apoptotic effects of vinorelbine against human squamous cell lung carcinoma cell line
Augments apoptotic effects of cisplatin against ovarian cancer and breast cancer cell lines
Has no effect on cytotoxic effects of paclitaxel against human ovarian cancer and breast cancer cell lines
Enhances antitumor effects of 5-FU and 5-FU plus oxaliplatin (FOLFOX) against colon cancer cells
Potentiates apoptosis induced by gemcitabine and paclitaxel in bladder cancer cells in culture
Potentiates antitumor activity of docetaxel against ovarian cancer cell lines
Increases antitumor effects of oxaliplatin against colorectal cancer cells in culture
Augments cytotoxic effects of gemcitabine on pancreatic adenocarcinoma cell line
Enhances the antitumor effects of gemcitabine against prostate cancer cells in culture
Potentiates cytotoxicity of cisplatin, etoposide, camptothecin, and doxorubicin against human and rat
Enhances antitumor effects of oxaliplatin against colorectal cancer cell lines
Enhanced the antitumor effects of vincristine and PDE4 inhibitors in B-CLL from patients
Enhances antitumor effects of 5-FU and FOLFOX against colon cancer cells
Augments effects of sulfinosine on multi drug resistant human non-small cell lung carcinoma cells
Potentiate effects of gemcitabine in pancreatic cancer cells
Sensitizes lung cancer cells to cisplatin-induced apoptosis in lung cancer cells
Potentiates the effect of thalidomide and bortezomib in multiple myeloma cells
Augments growth inhibitory effects of celecoxib against colorectal cancer in rats
Enhances antitumor effects of oxaliplatin against colorectal cancer in mice
Potentiates antitumor activity of gemcitabine against pancreatic cancer in mice
Potentiates antitumor activity of docetaxel against ovarian cancer in mice
Enhances the antitumor effects of gemcitabine against prostate cancer in mice
Potentiates the effect of thalidomide and bortezomib against multiple myeloma in nude mice
Antagonizes apoptotic effects of camptothecin, mechlorethamine, and doxorubicin in human breast
Reduces nephrotoxicity of cisplatin in rats
Antagonizes apoptotic effects of cyclophosphamide in mice
aAbbreviations are as follows: 5-FU, 5-fluorouracil; HeLa, a cervical carcinoma cell line derived from Henrietta Lacks; SiHa, a cervical
ability of curcumin in multiple cancers and have provided ev-
ment with curcumin and 5-FU in HT-29 cells. The importance
idence for curcumin’s use singly or as an adjunct to current
of the Cox-2 pathway in mediating efficacy of curcumin was
chemotherapeutic drugs. Table 1 summarizes these data in or-
further highlighted in another report in which curcumin po-
der of appearance of these reports in the published literature.
tentiated the growth inhibitory effect of celecoxib in multi-ple colon cancer cell lines (33). In a follow-up study, these
Colon Cancer
investigators determined the chemopreventive effects of cele-
Cancers of the gastrointestinal tract, especially colon can-
coxib and curcumin alone and in combination using the 1,2-
cer, remain leading causes of cancer-related deaths in the devel-
dimethylhydrazine (DMH) rat model (34). In this in vivo study,
oped nations, including the United States (28). Although current
curcumin augmented the growth inhibitory effect of celecoxib
chemotherapeutic regimens targeting colon cancer have contin-
as indicted by significantly fewer aberrant crypt foci in the com-
uously evolved and have significantly improved survival rates
bined curcumin and celecoxib group compared to when these
by limiting the spread of metastatic disease over the last decade,
agents were fed individually (34). Such effects of curcumin are
a large majority of patients develop chemoresistance to these
not limited to colon cancer, but others have shown similar results
platinum-based and/or 5-fluorouracil (5-FU)-based drug regi-
in gastric (35), pancreatic (36–38), and liver cancers (39) as well.
mens over the course of chemotherapy. Use of curcumin singlyor in combination with chemotherapeutic drugs may help over-come some of the resistance issue and improve the efficacy of
Gastric Cancer
current chemotherapeutic drugs. In one study, Howells and col-
Using physiologically relevant and very small doses of cur-
leagues (29) investigated the antiproliferative potential of both
cumin together with 5-FU, much stronger G2/M cell cycle block
curcumin and oxaliplatin singly and in combination in normal
was achieved in AGS gastric cancer cells compared to the block
colonic (HCEC) and colon cancer cell lines (HT29, p53 mutant
in control groups in which cells were treated with single agents
and HCT116, p53 wild type). Both curcumin and oxaliplatin dis-
played significant antiproliferative potential in both HT29 andHCT116 cells; and the order of sensitivity to oxaliplatin wasHCT116>HT29>HCEC, whereas order of sensitivity to cur-cumin was HT29>HCT116>HCEC. Apoptosis was enhanced
Pancreatic Cancer
by both compounds, and up to 16-fold increase in expression
Pancreatic adenocarcinoma is a fatal disease with very
of p53 protein was observed when the two agents were used
poor prognosis. Data indicate that specific Cox-2 inhibitors
in combination. This study suggested that when used in com-
(such as celecoxib) may have some promise in this disease.
bination with oxaliplatin, curcumin may enhance efficacy of
However, sustained and robust Cox-2 inhibition for the long
this drug in both p53 mutant and wild type colorectal tumors.
term is a practical challenge in managing these individuals. In
Since curcumin in its free form may be poorly absorbed in the
this regard, Lev-Ari et al (36) questioned whether curcumin
gastrointestinal tract, a liposomal encapsulated preparation of
may potentiate growth inhibitory effects of a celecoxib in a
curcumin was evaluated individually and in combination with
panel of Cox-2-expressing (P-34) and low/nonexpressing (MIA
oxaliplatin in LoVo and Colo205 human colorectal cancer cell
PaCa and Panc-1) human pancreatic cell lines. Curcumin syn-
lines (30). Liposomal curcumin treatment showed a synergistic
ergistically augmented growth inhibition of celecoxib in Cox-
effect with oxaliplatin at a ratio of 4:1 in LoVo cells in vitro
2-expressing cell lines, suggesting that celecoxib may be used
and a significant tumor growth inhibition in Colo205 and LoVo
at much lower and safer concentrations. The same group of in-
xenografts in mice, substantiating the chemosensitizing ability
vestigators later reported similar effects of curcumin when used
in combination with the first-line chemotherapeutic agent gem-
When curcumin treatment was evaluated in conjunction with
citabine in pancreatic cancer cells (36). These data were further
either 5-FU alone or 5-FU + oxaliplatin (FOLFOX), it resulted
substantiated by other studies in which it has been demonstrated
in significantly greater growth inhibition and increased apopto-
that curcumin potentiated the antitumor effects of gemcitabine in
sis in HCT116 and HT29 colon cancer cells than that caused
cultured pancreatic adenocarcinoma cells by suppressing cellu-
by curcumin, 5-FU, curcumin + 5-FU, or FOLFOX alone (31).
lar proliferation and activating NF-κB and other genetic targets
Such effects were associated with decreased expression and
of the NF-κB signaling pathway (37,38,40) In vivo studies with
activation of EGFR, HER-2, HER-3, and insulin-like growth
tumors from nude mice injected with pancreatic cancer cells and
factor 1 receptor (IGF-1R), together with their downstream sig-
treated with both curcumin and gemcitabine showed significant
naling targets such as Akt and cyclooxygenase-2 (Cox-2) (31).
reduction in tumor volume, Ki-67 proliferation index, NF-κB
It was concluded that the potentiation of curcumin’s effect with
activation, expression of NF-κB gene products [cyclin D1, c-
FOLFOX were due to attenuation of EGFR and IGF-1R sig-
myc, B-cell non-Hodgkin lymphoma-2 (Blc-2), Bcl extra large
naling pathways (31). Similarly, Du and coworkers (32) re-
(Bcl-xl), CIAP-1, Cox-2, matrix metalloproteinase (MMP), and
cently demonstrated synergistic inhibition of cell growth and
vascular epithelial growth factor (VEGF)], and suppression of
sixfold reduction in Cox-2 expression after combination treat-
angiogenesis compared to tumors from control animals (38). Liver Cancer
mechlorethamine-, and doxorubicin-induced apoptosis of MCF-
While investigating antitumor effects of curcumin, singly or
7, MDA-MB-231, and BT-447 human breast cancer cells
together with cisplatin or doxorubicin, it was noticed that the
(45). In animal experiments, curcumin significantly inhibited
combination of curcumin with cisplatin resulted in synergis-
cyclophosphamide-induced tumor regression, suggesting that
tic activity against liver cancer; whereas with doxorubicin, the
dietary curcumin can inhibit chemotherapy-induced apoptosis
effects were at best additive (39). Such effects were in part
via inhibition of ROS generation and blocking JNK signaling.
mediated by downregulation of expression of different genesincluding c-myc, Bcl-xl, c-IAP-2, NAIP, and XIAP (39). Ovarian Cancer
High levels of certain serum proinflammatory cytokines, in-
Prostate Cancer
cluding IL-6, have been associated with poor prognosis and
The literature on similar potential for curcumin in other
cisplatin resistance in multiple human cancers. Since curcumin
solid organ malignancies has grown continuously over the last
inhibits production of many cytokines, its effects were studied
decade. In this context, while studying the modulatory effects of
in CAOV3 ovarian cancer cells, singly, and in combination with
curcumin on the cytotoxic effects of chemotherapeutic agents
cisplatin (46). As anticipated, curcumin inhibited IL-6 produc-
(5-FU, doxorubicin, and paclitaxel) in androgen-independent
tion in cisplatin-treated cells, suggesting that one mechanism
prostate cancer cell lines (PC-3 and DU-145), a significant
for curcumin action is by reduction of autologous production of
degree of G1-cell cycle arrest was observed in the combina-
IL-6, which has potential for enhancing drug sensitivity in mul-
tion treatment group (41). It was proposed that such cell cycle
tiple human cancers. In another study, curcumin when given
changes may be associated with an increase in p21 and C/EBP
together with docetaxel to HeyA8 and HeyA8-MDR athymic
β and inhibition of constitutive and TNFα-induced NF-κB ac-
mice, significantly reduced tumor growth, cellular proliferation,
tivation (41). Curcumin treatment in combination with gemc-
and microvessel density compared to controls, emphasizing the
itabine in PC-3 cells inhibited growth and increased apoptosis
potential of curcumin-based therapies in patients with ovarian
but via downregulation of MDM2, an ubiquitin E3 ligase of
p53 gene (42). In further support of these data, when experi-ments were performed in tumor-bearing nude mice, curcumin
Cervical Cancer
inhibited growth of PC3 xenografts and enhanced the antitumor
NF-κB activation plays a pivotal role in drug-mediated apop-
efficacy of gemcitabine and radiation (42).
tosis and possible resistance in various human cancers. Usinga cervical cancer model of HeLa and SiHa cells that differ in
Breast Cancer
their response to cisplatin treatment, it was demonstrated that
Presently, other than radiation and chemotherapy, there is
SiHa cells, which are more resistant to cisplatin, showed much
no effective therapy for metastatic breast cancer. Curcumin is a
lesser cell viability when NF-κB binding was blocked by cur-
potent NF-κB suppressor, while most conventional chemother-
cumin (48). Such effect was not evident in cisplatin-responsive
apeutic agents activate NF-κB. Keeping this in mind, Aggarwal
HeLa cells. These data suggest that NF-κB may contribute to
and colleagues (43) hypothesized that curcumin potentiates the
cisplatin-induced chemoresistance in cervical cells and high-
effects of chemotherapy in advanced breast cancer and inhibits
lights the potential applicability of combination therapy with
lung metastasis. Using paclitaxel (Taxol)-resistant breast cancer
NF-κB inhibitors such as curcumin in this scenario. Curcumin
cells and a human breast cancer xenograft model, they showed
was also shown to downregulate taxol-induced activation of NF-
that curcumin inhibited paclitaxel-induced NF-κB activation,
κB and phosphorylation of serine/threonine kinase Akt in 293
and these effects were mediated through inhibition of IκBα ki-
cervical cells and 293 embryonic kidney cells (49).
nase activation and IκBα phosphorylation and degradation (43). In addition, curcumin also suppressed the paclitaxel-induced
Lung Cancer
expression of several antiapoptotic (XIAP, IAP-1, IAP-2, Bcl-
Due to toxicity concerns and older age, some lung cancer
2, and Bcl-xl), proliferative (Cox-2, c-myc, and cyclin D1),
patients are not suited for classical cancer chemotherapy. Com-
and metastatic (VEGF, MMP-9, and ICAM-1) proteins (43).
bination approaches using phytochemicals such as curcumin
Curcumin also inhibited the mono-ubiquitination of the
are being advocated as a possible alternative to get around some
FANCD2 protein and sensitized ovarian and breast tumor cells
of the practical constraints posed by conventional chemother-
lines to cisplatin through enhanced apoptotic death (44).
apeutic drugs. Pretreatment of squamous cell lung carcinoma
Generation of reactive oxygen species (ROS) and activa-
H520 cells with curcumin, followed by chemotherapy using
tion of the c-Jun N-terminal protein kinase (JNK) pathway
vinorelbine, enhanced the apoptotic capacity of this drug (50),
is a frequent manifestation of proapoptotic ability offered by
suggesting that curcumin can act as an adjuvant chemotherapeu-
many chemotherapeutic drugs. Somasundaram et al. (45) asked
tic agent and enhance the chemotherapeutic drugs in a subset of
whether curcumin may antagonize the antitumor effects of var-
ious chemotherapeutic drugs in both cultured cells and an ani-
MDR is a frequent limiting factor for a successful chemother-
mal model of breast cancer. Curcumin inhibited camptothecin-,
apeutic regimen. However, data indicate that curcumin can
overcome MDR induced by sulfinosine in NCI-H460/R non-
CURCUMIN AS A RADIOSENSITIZER
small-cell lung carcinoma cells (51). Combination of curcumin
In addition to its role as a potent chemosensitizer, increasing
and sulfinosine produced more pronounced S and G2/M cell
evidence suggests that curcumin can also function as a very
cycle arrest compared to treatment with these agents individ-
promising radiosensitizing agent in a wide variety of human
ually. When cisplatin was used as a chemotherapeutic drug,
curcumin sensitized cisplatin-induced apoptosis in non-small-cell lung cancer H460 cells via downregulation and degradation
Colon Cancer
Radiation therapy, alone or in conjunction with chemother-
apy, is one of the preferred modalities in patients with coloncancer who develop resistance to individual chemotherapies. Brain and Bladder Cancers
Mechanisms for developing such resistance are unclear, but it
Since NF-κB serves as nexus in human cancers, in another
has been suggested that some of this resistance may be mediated
interesting study by Kamat and coworkers (53), it was shown
by NF-κB and its gene products. Because curcumin has been
that curcumin blocked both gemcitabine- and TNFα-induced
shown to suppress activation of NF-κB, it was hypothesized
activation of NF-κB in KU-7 bladder cancer cells. Curcumin’s
that curcumin may sensitize colon cancer to gamma-irradiation
ability to overcome glioma cell resistance and chemoresistance
in a xenograft nude mice model (60). Curcumin significantly
was investigated in a panel of human (T98G, U87MG, and
enhanced the effectiveness of radiation therapy by prolonging
T67) and rat (C6) glioma cell lines (54). It was demonstrated
tumor regrowth, by reducing Ki-67 proliferation index, and by
that curcumin sensitized glioma cells to several chemotherapeu-
suppressing NF-κB activity and its gene products (60). Com-
tic agents (cisplatin, etoposide, camptothecin, and doxorubicin)
bined curcumin and radiation treatment also suppressed angio-
and radiation by reducing the expression of Bcl-2 and IAP fam-
ily member proteins as well as DNA repair enzymes (MGMT,
Prostate Cancer
DNA-PK, Ku70, Ku80, and ERCC-1) (54).
Curcumin has also been shown to have radiosensitizing ef-
fects in prostate carcinoma. In this regard, curcumin signif-icantly improved radiation-induced clonogenic inhibition and
Hematological Cancers
apoptosis in cultured prostate cancer PC3 cells (61). Curcumin,
As is the case with solid organ malignancies, NF-κB also
in combination with radiation treatment, inhibited TNFα-
plays a central role in cell survival and proliferation in hema-
mediated NF-κB activity, downregulated Bcl-2 protein, but had
tological cancers. As curcumin is a potent NF-κB inhibitor,
no effect of Bax protein in PC3 cells. Collectively, these data
Bharti et al. (55) explored the effects of curcumin in multiple
suggest that curcumin is a potent radiosensitizing agent, and
myeloma (MM) cell lines, which express NF-κB in a constitu-
it acts by negating the effects of radiation-induced prosurvival
tively active manner. Curcumin induced significant apoptosis,
genes in prostate cancer. In another study, curcumin showed anti-
suppressed the constitutive IκBα phosphorylation, and down-
cancer and radiosensitization effects by downregulating MDM2
regulated several NF-κB gene products. Similarly, in a recent
levels in cultured PC3 prostate cancer cells, as well as growth
study, when chemosensitizing effects of curcumin were eval-
of xenografts in nude mice, by enhancing the antitumor effects
uated in cell culture and xenograft model of MM, curcumin
overcame chemoresistance and sensitized MM cells to thalido-mide and bortezomib by downregulating NF-κB and its gene
Cervical Cancer
products (56). These data provided a molecular basis for treat-
Cervical cancer is the second leading cancer among women,
ment of MM patients with curcumin, that is, its ability to down-
and these cancers are typically very radioresistant. Conse-
regulate NF-κB. Curcumin also potentiated antitumor effects
quently, for locally advanced disease, radiation therapy is often
of sodium butyrate by reducing overall cell growth in human
used in conjunction with chemotherapy, which is severely toxic.
erythroleukemic cells (57). In a more recent study, curcumin
Curcumin may be an ideal adjunct for radiation therapy if it has
treatment reduced basal NF-κB levels and augmented both vin-
radiosensitizing properties. In support of this, it was recently
cristine and PDE4 inhibitor rolipram-induced apoptosis in cul-
demonstrated that pretreatment of 2 cervical cancer cell lines
tured primary chronic lymphocytic leukemia cells (58). Taken
HeLa and SiHa with curcumin prior to ionizing radiation re-
together, all of these studies have indicated a potent chemosensi-
sulted in radiosensitization of cancer cells but had no effect on
tizing potential of curcumin in overcoming resistance afforded
normal human diploid fibroblasts (62). Such effects of curcumin
by standard chemotherapeutic drugs. In a more recent study,
were due to its ability to sensitize cancer cells for increased pro-
curcumin treatment reduced basal NF-κB levels and augmented
duction of ROS, which in turn led to activation of ERK1 and
both vincristine and PDE4 inhibitor rolipram-induced apopto-
ERK2. These data provide a novel mechanism of curcumin-
sis in cultured primary chronic lymphocytic leukemia (B-CLL)
mediated radiosensitization and suggest that curcumin may be
an effective radiosensitizer in cervical cancer.
Curcumin potentiates the effect of radiotherapya
Inhibits UV-radiation induced oxidative stress and apoptotic changes in epidermal carcinoma cells
Inhibits apoptotic effects of photodynamic therapy against human epidermal carcinoma cells
Enhances the antitumor effects of irradiation against prostate cancer cells in culture
Radiosensitizes squamous cell carcinoma cells in culture
Enhances the antitumor effects of irradiation against prostate cancer cells in culture
Potentiates cytotoxicity of radiation (5 Gy) against human and rat glioma cell lines
Increases anti-proliferative effects of radiation (UVA and visible light) against human keratinocyte cell line
Increases apoptotic effects of radiation (UVB) against human keratinocyte cell line
Enhances antitumor effects of radiation (2 Gy) against human neuroblastoma cells in culture
Enhances antitumor effects of ionizing radiation against cervical carcinoma cells in culture
Enhances the antitumor effects of irradiation against prostate cancer cells in mice
Enhances antitumor effects of fractionated radiation therapy (4 Gy) against colorectal cancer in mice
In combination with visible light inhibits tumor growth in xenograft tumor model
aAbbreviations are as follows: UV, ultraviolet; Gy, gray units; UVA, UV A light; UVB, UV B light. Brain Cancer
had similar radiosensitization effect in inhibiting photodynamic
Malignant gliomas are a debilitating class of neoplasms that
treatment (PDT)-induced caspase activation in A431 cells (65).
are often resistant to standard radiation and chemotherapeu-tic regimens. High levels of NF-κB and AP-1 expression ingliomas is in part responsible for increased chemoresistance andradioresistance. Due to its strong NF-κB inhibitory properties,Dhandapani and colleagues (54) determined whether curcumin
Skin Cancer
can sensitize human and rat glioma cells by shortening their
One of the unfortunate but relatively frequent manifestations
survival in cultured cells. Interestingly, combined curcumin and
of excessive exposure to UV or visible light is the possibil-
radiation treatment of T98G, U87MG, and T67 cells reduced
ity of skin cancers. Because curcumin has traditionally been
cell survival and inhibited AP-1 and NF-κB signaling pathways,
used for different cosmetic applications and has been proposed
suggesting a role for curcumin as an adjunct to traditional radia-
to possess skin-healing properties, multiple studies have hy-
tion therapy in brain cancers (54). Similar effects were indepen-
pothesized that some of its effect may be attributable to its
dently validated in another study in which curcumin inhibited
radiosensitizing ability. Experimental evidence in this regard
NF-κB-mediated radioprotection and modulated expression of
was provided in a recent study in which cultured human skin
apoptosis-related genes in human neuroblastoma cells (63).
keratinocytes treated with curcumin in combination with UVor visible light increased apoptosis and fragmented cell nuclei,activated caspase-9 and caspase-8, and inhibited NF-κB activ-
Epidermal Cancer
ity (66). Subsequently, these investigators performed similar
Ultraviolet (UV) light is known to be a trigger for apop-
studies in an animal model system and reported that curcumin
totic signaling, which results in induction of caspase-dependent
in combination with visible light inhibited tumor growth in a
biochemical changes in cells. UV irradiation can not only ac-
xenograft tumor model (67). Curcumin-induced radiosensitiza-
tivate caspase-3 but also cleave and activate p21-activated ki-
tion resulted in increased apoptosis, and this correlated with
nase 2 (PAK2) in human epidermoid carcinoma (A431) cells.
reduced Ki-67 expression, as well as lower levels of extracel-
Given the anti-inflammatory and antioxidant potential of cur-
lular regulated kinases (ERK1 and 2), and epidermal growth
cumin, curcumin was studied for its ability to prevent UV
factor receptor (EGFR). Park and Lee (68) showed similar re-
irradiation-induced apoptotic changes, JNK activation, caspase-
sults when curcumin was combined with photodynamic therapy
3-activation, and cleavage/activation of PAK2 in the A431
in which synergism was observed between curcumin and UVB-
cell line (64). Curcumin significantly inhibited UV irradiation-
irradiation in HaCaT cells. Taken together, these results indicate
induced generation of ROS and blocked JNK activation, cas-
that a combination of curcumin and light is a possible therapeutic
pase activation, and subsequent apoptotic changes (64). In a
approach to enhance the overall efficacy of treatment regimens
follow-up study, these investigators demonstrated that curcumin
Squamous Cell Cancer
gested a safe use of curcumin and CAPE in combination with
Radiosensitization of cancer cells is in part dictated by the
distribution of cells in various phases of the cell cycle, with
Curcumin has also been used to attenuate acute Adriamycin-
much better responses in cells that are in G2/M phase. It seems
induced myocardial (11) and nephrotoxicity (71) in rats. In these
prudent that if cancer cells are pretreated with curcumin, this
studies, curcumin pretreatment reversed the increase in lipid
may result in enhanced radiosensitization as one of its secondary
peroxidation and catalase, with simultaneous decrease in glu-
effects. Khafif et al (69) studied whether curcumin can sensitize
tathione content and glutathione peroxidase activity caused by
squamous cell carcinoma cells exposed to 1 to 5 Gy of ionizing
Adriamycin in cardiac tissues of rats (11). Curcumin pretreat-
irradiation. Curcumin treatment of cells exposed to such doses
ment also restored renal function in Adriamycin-treated rats
of ionizing radiation decreased cell growth and reduced ability
by inhibiting Adriamycin-induced increase in urinary excretion
to form colonies, an effect that may have been partly due to
of N-acetyl-beta-D-glucosaminidase, fibronectin, glycosamino-
curcumin’s ability to block cells in G2/M cell cycle phase (69).
glycan, and plasma cholesterol (71). These data indicate thatcurcumin may serve as an adjunct to Adriamycin therapy byreducing myocardial toxicity and nephrosis.
In another model of nephrotoxicity, when cisplatin was used
CURCUMIN AS A CHEMOPROTECTOR
as a chemotherapeutic drug, pretreatment of rats with various
NF-κB activation is a common feature of most cancers, and
does of curcumin protected against cisplatin-induced nephro-
inhibiting its activation and suppressing its downstream gene
toxicity by preventing alterations in various biochemical and
targets is one of the goals for most cancer preventive and ther-
inflammatory markers (59). Oral treatment with curcumin 10
apeutic approaches. Although many of the current chemother-
days before, or daily after a single intratracheal installation
apeutic drugs may inhibit NF-κB in tumor cells, their toxic
of bleomycin, protected against bleomycin-induced pulmonary
effects on surrounding peritumoral mucosa and other normal
fibrosis, as evidenced by protection against changes in total
cells is one of the limiting factors and concerns. However, pre-
lung hydroxyproline, alveolar macrophage production of TNFα
treatment of cancer patients with the potent NF-κB inhibitor
superoxide, and nitric oxide (72). Collectively, these reports
curcumin may preferentially affect tumor cells and at the same
clearly highlight the chemoprotective role of curcumin and sup-
time afford sufficient protection for normal cells (Table 3).
port its potential use as an adjunct to chemotherapy for multiple
One of the limitations of cisplatin-based chemotherapy is
development of nephrotoxicity. Data suggest that increased in-flammatory and oxidative stress may in part be responsible forcisplatin-induced acute renal failure. Because curcumin is a
CURCUMIN AS A RADIOPROTECTOR
promising anti-inflammatory and antioxidant, Kuhad et al. (59)
Accumulating evidence suggests that curcumin may not only
investigated the effect of curcumin in an animal model of re-
have a chemoprotective role, but several studies have indi-
nal injury induced by cisplatin. Curcumin treatment reverted all
cated its potential as a radioprotective agent as well (Table 3).
cisplatin-induced alterations including significant lowering of
Parshad and colleagues (73) were among the first to suggest a
serum TNFα levels, restoring renal function, reducing lipid per-
radioprotective role for curcumin when they studied radiation-
oxidation, and enhancing the levels of glutathione and activities
induced chromosomal defects in human skin fibroblasts and
of superoxide dismutase and catalase (59).
blood lymphocytes. It was demonstrated that pretreatment with
Van’t Land and colleagues (70) hypothesized that in gastroin-
curcumin and other plant polyphenols to cultured skin fibrob-
testinal cancers, mucosal barrier injury is initiated and propa-
lasts or PHA-stimulated lymphocytes reduced the frequency of
gated by multiple proinflammatory cytokines and chemokines
radiation-induced chromatid breaks. It was surmised that such
as well as NF-κB-regulated mediators. To address this, these
effects of curcumin were due to its strong antioxidant capac-
researchers undertook a study of curcumin’s ability to inhibit
ity, which scavenged toxic free radicals induced by radiation
NF-κB in the onset of arabinoside cytosine- and methotrexate-
exposure of these cells (73). Similar effects of curcumin on
induced mucosal barrier injury in human intestinal epithelial
blood cells were investigated in a later report in which it was
(IEC-6) cells. Both drugs resulted in NF-κB activation as well
shown that pretreatment of cultured peripheral blood lympho-
as induction of TNFα and other downstream targets (70). Inter-
cytes with very low doses of curcumin (1–10 µg/ml) protected
estingly, NF-κB inhibition increased the susceptibility of IEC-6
against even up to 2 Gy dose of gamma radiation (74). In this
cells to the drug-induced cell death upon addition of caffeic acid
study, curcumin pretreatment protected against increases in mi-
phenethyl ester (CAPE) but not that induced by curcumin. In
cronuclei and dicentric nuclei formation, increases in lipid per-
addition, in an animal model of methotrexate-induced mucosal
oxidation, and decreases in superoxide dismutase, catalase, and
barrier injury, treatment with curcumin resulted in NF-κB inhi-
glutathione peroxidase activities induced by radiation treatment
bition and partial amelioration of villous atrophy. These results
(74). Findings from the study by Kunwar et al (75) reiterated
provided evidence that inhibition of NF-κB does not necessarily
the radioprotective role of curcumin when these investigators
increase intestinal side effects of the anticancer drugs and sug-
reported delayed activation of PKCδ and NF-κB in splenic
Curcumin protects from the toxic effects of chemotherapy and radiotherapy
Protects against radiation-induced DNA damage in cultured human cells
Reduces apoptotic effects of arabinoside cytosine (Ara-C) against human intestinal epithelial cells
Enhances radioprotection in cultured human lymphocytes
Enhances radioprotection in mice splenic lymphocytes
Protects against gamma radiation induced chromosomal damage in mice
Reduces lung toxicity of whole-body irradiation in rats
Reduces genotoxicity of whole-body irradiation in mice
Reduces cardiotoxicity of doxorubicin in rats
Prevents doxorubicin nephrotoxicity in rats
Inhibits bleomycin-induced pulmonary fibrosis in rats
Decreases acute toxicity of whole-body irradiation in rats
Reduces radiation-induced oral mucositis in rats
Reduces mucosal barrier injury from methotrexate in rats
Enhances repair of wounds in mice exposed to whole-body γ -irradiation
Enhances repair of wounds in mice exposed to hemibody γ -irradiation
Protects against radiation-induced cutaneous cytotoxicity in mice
Reduces nephrotoxicity of cisplatin in rats
lymphocytes by curcumin and a curcumin:copper complex (1:1
Wound healing following radiation therapy is a frequent con-
ratio) in radiation-exposed lymphocytes.
cern, as radiation treatment often disrupts normal response to
In addition to in vitro evidence, data from several animal
injury and results in delayed recovery periods. Radioprotective
studies have now confirmed that curcumin has a strong ra-
effects of curcumin have been investigated on wound healing in
dioprotective function. Abraham and colleagues (76) used the
mice exposed to 2 to 8 Gy doses of whole-body gamma radiation
mouse bone marrow micronucleus test to interrogate the pro-
(81,82). Pretreatment with curcumin significantly enhanced the
tective role of 3 dietary agents including curcumin in mice ex-
rate of wound contraction; shortened wound healing duration;
posed to gamma radiation. The data from this study indicated
and increased collagen synthesis and hexosamine, DNA, and
that oral administration of curcumin 2 h before or immediately
nitric oxide formation (81). In a related study, the same group of
after exposing the animals to whole-body, high-energy gamma
researchers used hemibody radiation exposure combined with
irradiation significantly reduced the frequency of micronucle-
curcumin pretreatment to make similar observations on wound
ated polychromatic erythrocytes (76). Similar protective effects
healing (83). In an effort to better understand these radioprotec-
were noticed in mice pretreated with curcumin before expo-
tive effects on a molecular level, it was shown that curcumin pre-
sure to gamma irradiation in which curcumin helped reduce the
treatment protected against radiation-induced acute and chronic
number of bone marrow cells with chromosomal aberrations
cutaneous toxicity in mice by decreasing gene expression of
and other chromosomal fragments (77).
inflammatory (IL-1, IL-6, IL-18, TNFα, and lymphotoxin-β)
Such radioprotective effects of curcumin were still notice-
and fibrogenic cytokine (TGFβ) at 21 days postradiation (84).
able when much higher radiation doses (up to 10 Gy) were used
Taken together, these studies have indicated a potential use of
in rats in which curcumin pretreatment significantly reduced the
curcumin as a radioprotective agent in patients with radiation-
number of micronucleated cells and inhibited superoxide dis-
mutase activity with a concomitant increase in catalase activityin liver tissues (78). Curcumin treatment for 3 days before and/or2 days after irradiation in female rats also inhibited levels of uri-
CLINICAL IMPLICATIONS AND CONCLUSIONS
nary 8-hydroxy-2 -deoxyguanosine and significantly decreased
Given the shortcomings of current chemotherapy and radia-
the incidence of mammary and pituitary tumors (79). In another
tion treatments for cancer management, it is obvious that such
study, curcumin treatment of animals exposed to localized ir-
treatments in the future must be combined with more effective
radiation of their tongues resulted in an overall improvement
and safer drugs/compounds. In this regard, given all the encour-
against radiation-induced oral mucositis (80).
aging evidence summarized in the previous sections, curcumin
seems to be an ideal, safe, and highly effective compound that
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Lasixstudie Ziel und Zweck Arbeitsanweisung zur Durchführung einer Lasixstudie im Anschluss an eineNierenszintigraphie. Anwendung Allgemeines Mit dem Einsatz von Furosemid (Lasix®) kann zwischen einer Abflussverzögerung durcheine Obstruktion oder infolge eines ektatischen Hohlraumsystems unterschieden werden. Indikationen Verzögerte Harnabflusssituation bei einer Nierenperfusi
‘Who in the name of heaven is Vivaldo?’ inquires Filippo Giordano, with slight impatience in his voice. ‘Vivaldi,’ corrects the man in a smart, perhaps slightly old-fash-ioned but still respectable tweed suit. He shifts rather uncomforta-bly on the chair that stands a shade too low before the impressive mahogany desk of Signore Giordano, adding, ‘Antonio Vivaldi was an extremely gifted