IJC

International Journal of Cancer

The dark side of curcumin

Estefana Burgos-Moron1, Jose Manuel Calderon-Montano1, Javier Salvador2, Antonio Robles3 and Miguel Lopez-Lazaro1
1

Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain

Oncology Unit, Hospital Universitario de Valme, Seville, Spain
3
Department of Pathology, Hospital Universitario de Valme, Seville, Spain
2

Curcumin is a yelloworange pigment obtained from the

plant Curcuma longa. The powdered rhizome of this plant,
called turmeric, is a common ingredient in curry powders
and has a long history of use in traditional Asian medicine
for a wide variety of disorders. In the last decade a large
number of reports have been published on the benecial
effects of curcumin, and it has repeatedly been claimed that
this natural product is efcient and safe for the prevention
and treatment of several diseases including cancer.13 It is
not surprising, therefore, that curcumin is currently sold as a
dietary supplement and that numerous clinical trials are
ongoing or recruiting participants to evaluate curcumin activity. But there is accumulating evidence that curcumin may
not be so effective and safe. Because such evidence is not
generally acknowledged, the purpose of this letter is to briey
review the negative properties of curcumin so that they can
be balanced against its benecial effects.
Most of the evidence that supports the therapeutic potential of curcumin is mainly based on in vitro studies in which
curcumin was tested at concentrations in the micromolar
range. Several reports have demonstrated, however, that the
plasma concentrations of curcumin in people taking relatively
high oral doses of this compound are very low, typically in
the nanomolar range (reviewed in Ref. 4). For instance, a
recent study examined the pharmacokinetics of a curcumin
preparation in 12 healthy human volunteers 0.2572 hr after
an oral dose of 10 or 12 g. Using a high-performance liquid
chromatography assay with a limit of detection of 50 ng
mL
1, only 1 subject had detectable free curcumin at any of
the time points assayed.5 The fact that curcumin also undergoes extensive metabolism in intestine and liver6,7 means that
high concentrations of curcumin cannot be achieved and
maintained in plasma and tissues after oral ingestion. This is
a major obstacle for the clinical development of this agent
and suggests that the therapeutic potential of oral curcumin
is limited. The low clinical efciency of curcumin in the
treatment of several chronic diseases such as Alzheimers disease and cardiovascular diseases has been discussed recently.8
As far as cancer is concerned, in vitro studies have demonstrated that cancer cells do not die unless they are exposed
to curcumin concentrations of 550 lM for several
hours.4,9,10 Because of its poor bioavailability, these concentrations are not achieved outside the gastrointestinal tract
when curcumin is taken orally. Because of its extensive metabolism in intestine and liver, these concentrations cannot
C 2009 UICC
Int. J. Cancer: 126, 17711775 (2010) V

be maintained for several hours in the gastrointestinal tract.

This suggests that the chemotherapeutic potential of oral curcumin is limited even for the treatment of cancers of the
gastrointestinal tract. Accordingly, when 15 patients with
advanced colorectal cancer were treated with curcumin at
daily doses of 3.6 g for up to 4 months, no partial responses
to treatment or decreases in tumor markers were observed.11
A search of the website www.clinicaltrials.gov in July 2009
showed 34 clinical trials using curcumin in a wide variety of
diseases, particularly in cancer. In some of these trials,
patients with several types of cancer are receiving or will
receive curcumin through the oral route. For instance, in an
ongoing Phase II clinical trial (NCT00094445), participants
with pancreatic cancer are receiving 8 g of curcumin by
mouth every day for several 8-week-periods. As discussed
before, the plasma concentrations of curcumin in people taking relatively high oral doses of curcumin are very low, typically in the nanomolar range. This means that the oral
administration of curcumin does not lead to cytotoxic concentrations outside the gastrointestinal tract. If one assumes
that tumor cell death is necessary to achieve an efcient therapeutic response, one should not expect a very positive outcome from this trial. A Phase II Trial is also recruiting participants to test if a daily oral dose of 8 g of curcumin can
improve the efcacy of the standard chemotherapy gemcitabine in patients with locally advanced or metastatic adenocarcinoma of the pancreas (NCT00192842). The rationale for
this trial is based on in vitro and in vivo data that suggest
that noncytotoxic concentrations of curcumin may sensitize
cancer cells to the effects of anticancer drugs such as gemcitabine.4,12 Although a daily dose of 1 g kg
1 of curcumin
increased the antitumor effects of gemcitabine in an orthotopic model of pancreatic cancer,12 this dose of curcumin
(e.g. 70 g in a 70-kg person) is almost 10 times higher than
that used in the clinical trial testing the combination of curcumin and gemcitabine (8 g). This makes the outcome of
this trial uncertain, as curcumin can either increase or reduce
the efciency of chemotherapy depending on the concentration at which it is used.4,13
Several strategies have been proposed to overcome the low
oral bioavailability of curcumin.4,1418 One of these strategies
has entered clinical trials and consists of using the black pepper alkaloid piperine (bioperine) to increase the bioavailability of curcumin.14 This strategy, however, should be used
cautiously, as piperine is a potent inhibitor of drug

Letters to the Editor

Dear Editor,

Letters to the Editor

1772

metabolism and may cause toxicity in people taking specic

drugs.8,19,20 In addition, it is important to note that any strategy
that increases the levels of curcumin in tissues will not only
increase the effectiveness of curcumin, but also its toxicity.
A relatively high number of reports suggests that curcumin may cause toxicity under specic conditions. In 1976
Goodpasture and Arrighi found that turmeric caused a doseand time-dependent induction of chromosome aberrations in
several mammalian cell lines; these alterations were observed
at concentrations of 10 lg mL
1.21 Accumulating data have
demonstrated since then that curcumin can induce DNA
damage and chromosomal alterations both in vitro and in
vivo at concentrations similar to those reported to exert benecial effect.2230 For instance, curcumin concentrations of 2.5
and 5 lg mL
1 were shown to induce DNA damage to both
the mitochondrial and nuclear genomes in cells.28 These
reports raise concern about curcumin safety, as the induction
of DNA alterations is a common event in carcinogenesis.
In 1993 the National Toxicology Program (USA) published
an extensive report on the toxic and carcinogenic properties of
an organic extract of turmeric, called turmeric oleoresin.31
This extract is commonly added to food items and contains a
percentage of curcumin (7985%) similar to that of commercial grade curcumin. Rats and mice were fed diets containing
several concentrations of turmeric oleoresin for 3 months and
2 years, and the possible toxic and carcinogenic effects were
evaluated. In the 2-year feeding studies, turmeric oleoresin
ingestion was associated with increased incidences of ulcers,
hyperplasia, and inammation of the forestomach, cecum and
colon in male rats and of the cecum in female rats. In female
mice, ingestion of diets containing turmeric oleoresin was
associated with an increased incidence of thyroid gland follicular cell hyperplasia. The report also concluded that there was
equivocal evidence of carcinogenic activity in female rats,
female mice, and male mice. These conclusions were based on
increased incidences of clitoral gland adenomas in female rats,
hepatocellular adenomas in female mice, and carcinomas of
the small intestine and hepatocellular adenomas in male mice.
The increased incidence of carcinomas of the small intestine
was observed in mice taking average daily doses of curcumin
of 0.2 mg kg
1 body weight.31 A recent report has also
shown that curcumin can promote lung cancer in mice.32
These negative effects of curcumin may be mediated by
several possible mechanisms. Evidence suggests that reactive
oxygen species (ROS) such as superoxide anion and hydrogen peroxide may play an important role in carcinogenesis.3336 This evidence is based on the facts that (i) ROS can
induce cell malignant transformation,3740 (ii) cancer cells
commonly have increased levels of ROS,4143 and (iii) the
malignant phenotype of cancer cells can be reversed by
reducing the cellular levels of ROS.40,4448 Experimental studies have demonstrated that, although low concentrations of
curcumin induce antioxidant effects, higher concentrations of
this compound increase the cellular levels of ROS.4,9,23,28,4953
The presence of 2 a,b-unsaturated ketones in the chemical

Letters to the Editor

structure of curcumin may also mediate some of its negative

properties. These chemical groups are known to react covalently with exposed thiol groups of cysteine residues of proteins through a reaction termed Michael addition. This reaction may explain, for instance, why curcumin generates ROS
by irreversibly modifying the antioxidant enzyme thioredoxin
reductase,49 why curcumin induces topoisomerase II-mediated DNA damage,10,54,55 and why curcumin inactivates the
tumor suppressor protein p53.56,57
Several other lines of evidence raise concern about curcumin safety. Curcumin was recently found to be an active iron
chelator in vivo and to induce a state of overt iron deciency
anemia in mice fed with diets poor in iron.58 This suggests
that curcumin has the potential to affect systemic iron metabolism, particularly in people with suboptimal iron status.58,59 Curcumin has also been shown to inhibit the activity
of the drug-metabolizing enzymes cytochrome P450, glutathione-S-transferase, and UDP-glucuronosyltransferase.8,6062
The inhibition of these enzymes in people taking curcumin
may lead to an undesired increase in the plasma concentrations of some drugs and cause toxicity.8
Although this letter is focused on the negative properties
of curcumin, it is important to note that there is evidence
suggesting that curcumin has benecial properties and could
be developed into a drug for the prevention and treatment of
diseases such as cancer.14 There are indeed numerous
reports showing benecial effects of curcumin in colon cancer, yet a potential role for curcumin in colon cancer has
been shown in few clinical studies only.63 In vivo data suggest
that curcumin may also exert benecial effects in organs outside the gastrointestinal tract;4 however, since curcumin does
not reach these organs at high concentrations, it is not clear
at this point whether these benecial effects are due to low
levels of curcumin, to metabolites of curcumin or to an
unknown indirect effect. To develop curcumin into a preventive or therapeutic drug, it is important to consider the dose
levels which elicit desirable/undesirable effects. Based on
human studies, it is generally recognized that curcumin does
not cause signicant short-term toxicity at doses up to 8 g
day
1; this dose of curcumin is considered suitable for trials
in which curcumin is administered for short periods of time.
This dose of curcumin is not completely harmless, however,
as human studies have shown that curcumin at doses ranging
from 0.9 to 3.6 g day
1 for 14 months originates some
adverse effects including nausea and diarrhea and causes an
increase in serum alkaline phosphatase and lactate dehydrogenase.11 Curcumin could be used at doses higher than 8 g
day
1 in situations in which no effective therapies exist (e.g.
advanced pancreatic cancer), as toxicity is acceptable in these
situations. But no human studies have been conducted to
date to test the dose levels which cause long-term toxicity.
This information would be valuable in the design of chemoprevention trials, in which chemopreventive agents are
administered for long periods of time and toxicity is not
always acceptable. Epidemiological data suggest that the
C 2009 UICC
Int. J. Cancer: 126, 17711775 (2010) V

lower incidence of gastrointestinal cancers in India may be

due to diets rich in curcumin, and it has been estimated that
the doses of curcumin in people consuming high amounts of
turmeric in their diet are 0.15 g day
1.63 In the absence of
long-term toxicity studies in humans, this dose may be considered suitable when curcumin is used for long periods of time.
This dose of curcumin is similar to that recommended by the
World Heath Organization,31 but 10 times lower than that
generally recommended by suppliers of curcumin supplements. The lack of long-term toxicity studies in humans
should not only be considered by health professionals, but also
by people taking supplements of curcumin (with and without
piperine) that are readily available in the market.
It is unfortunate that curcumin is regarded in the scientic literature as efcient and safe when its efciency and
safety have not yet been proven. The fact that curcumin is a
common dietary constituent is not enough to prove its safety,
as other common dietary constituents have shown toxicity
when used as dietary supplements.64 The fact that no major
toxicity has been found in short-term studies in humans is not
a proof of curcumin safety either. For a drug to be safe, it
must also be devoid of long-term toxicity, and the most complete long-term toxicity study conducted to date raises concern
about curcumin safety.31 In addition, the effectiveness of a
drug is usually established by randomized, placebo-controlled,
double-blind clinical trials, and no such trials have shown curcumin to be effective so far.8 Finally, the fact that the number
of studies showing positive effects of curcumin is much higher
than that showing negative effects does not necessarily mean
that the benet-risk ratio of curcumin is shifted towards the
benet; it may just indicate that there are more researchers
evaluating the benecial effects of curcumin than evaluating its
toxicity. It is the opinion of the authors that future research is
needed to establish the benet-risk prole of curcumin. In the
meantime, we believe that it is important to acknowledge the
negative properties of curcumin so that the use of curcumin is
not based on unbalanced information.
Yours sincerely,
Estefana Burgos-Moron
Jose Manuel Calderon-Montano
Javier Salvador
Antonio Robles
Miguel Lopez-Lazaro

References
1.

2.

3.

4.

Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB.

Curcumin and cancer: an old-age disease with an age-old
solution. Cancer Lett 2008;267:13364.
Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as
Curecumin: from kitchen to clinic. Biochem Pharmacol 2008;75:
787809.
Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells:
how many ways can curry kill tumor cells selectively? AAPS J 2009;
3:495510.
Lopez-Lazaro M. Anticancer and carcinogenic properties of
curcumin: considerations for its clinical development as a cancer

C 2009 UICC
Int. J. Cancer: 126, 17711775 (2010) V

5.

6.

7.

8.
9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

chemopreventive and chemotherapeutic agent. Mol Nutr Food Res

2008;52(Suppl 1):S10327.
Vareed SK, Kakarala M, Rufn MT, Crowell JA, Normolle DP,
Djuric Z, Brenner DE. Pharmacokinetics of curcumin conjugate
metabolites in healthy human subjects. Cancer Epidemiol Biomarkers
Prev 2008;17:14117.
Ireson C, Orr S, Jones DJ, Verschoyle R, Lim CK, Luo JL, Howells L,
Plummer S, Jukes R, Williams M, Steward WP, Gescher A.
Characterization of metabolites of the chemopreventive agent
curcumin in human and rat hepatocytes and in the rat in vivo, and
evaluation of their ability to inhibit phorbol ester-induced
prostaglandin E2 production. Cancer Res 2001;61:105864.
Ireson CR, Jones DJ, Orr S, Coughtrie MW, Boocock DJ, Williams
ML, Farmer PB, Steward WP, Gescher AJ. Metabolism of the cancer
chemopreventive agent curcumin in human and rat intestine. Cancer
Epidemiol Biomarkers Prev 2002;11:10511.
Mancuso C, Barone E. Curcumin in clinical practice: myth or
reality? Trends Pharmacol Sci 2009;30:3334.
Syng-Ai C, Kumari AL, Khar A. Effect of curcumin on normal and
tumor cells: role of glutathione and bcl-2. Mol Cancer Ther 2004;3:
11018.
Lopez-Lazaro M, Willmore E, Jobson A, Gilroy KL, Curtis H, Padget
K, Austin CA. Curcumin induces high levels of topoisomerase I- and
II-DNA complexes in K562 leukemia cells. J Nat Prod 2007;70:
18848.
Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt
HR, Marczylo TH, Morgan B, Hemingway D, Plummer SM,
Pirmohamed M, Gescher AJ, Steward WP. Phase I clinical trial of
oral curcumin: biomarkers of systemic activity and compliance. Clin
Cancer Res 2004;10:684754.
Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J,
Aggarwal BB. Curcumin potentiates antitumor activity of
gemcitabine in an orthotopic model of pancreatic cancer through
suppression of proliferation, angiogenesis, and inhibition of nuclear
factor-{kappa}b-regulated gene products. Cancer Res 2007;67:
385361.
Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY,
Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced
apoptosis in models of human breast cancer. Cancer Res 2002;62:
386875.
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS.
Inuence of piperine on the pharmacokinetics of curcumin in
animals and human volunteers. Planta Med 1998;64:3536.
Li L, Braiteh FS, Kurzrock R. Liposome-encapsulated curcumin:
in vitro and in vivo effects on proliferation, apoptosis, signaling,
and angiogenesis. Cancer 2005;104:132231.
Bisht S, Feldmann G, Soni S, Ravi R, Karikari C, Maitra A, Maitra A.
Polymeric nanoparticle-encapsulated curcumin (nanocurcumin): a
novel strategy for human cancer therapy. J Nanobiotechnology 2007;5:3.
Kurien BT, Scoeld RH. Oral administration of heat-solubilized
curcumin for potentially increasing curcumin bioavailability in
experimental animals. Int J Cancer 2009;125:19923.
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB.
Bioavailability of curcumin: problems and promises. Mol Pharm
2007;4:80718.
Atal CK, Dubey RK, Singh J. Biochemical basis of enhanced drug
bioavailability by piperine: evidence that piperine is a potent
inhibitor of drug metabolism. J Pharmacol Exp Ther 1985;232:
25862.
Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm
MF. Piperine, a major constituent of black pepper, inhibits human
P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:64550.
Goodpasture CE, Arrighi FE. Effects of food seasonings on the cell
cycle and chromosome morphology of mammalian cells in vitro with
special reference to turmeric. Food Cosmet Toxicol 1976;14:914.

Letters to the Editor

1773

Letters to the Editor

Letters to the Editor

1774

22. Giri AK, Das SK, Talukder G, Sharma A. Sister chromatid exchange
and chromosome aberrations induced by curcumin and tartrazine on
mammalian cells in vivo. Cytobios 1990;62:1117.
23. Ahsan H, Hadi SM. Strand scission in DNA induced by curcumin in
the presence of Cu(II). Cancer Lett 1998;124:2330.
24. Sakano K, Kawanishi S. Metal-mediated DNA damage induced by
curcumin in the presence of human cytochrome P450 isozymes.
Arch Biochem Biophys 2002;405:22330.
25. Nair J, Strand S, Frank N, Knauft J, Wesch H, Galle PR, Bartsch H.
Apoptosis and age-dependant induction of nuclear and
mitochondrial etheno-DNA adducts in Long-Evans Cinnamon (LEC)
rats: enhanced DNA damage by dietary curcumin upon copper
accumulation. Carcinogenesis 2005;26:130715.
26. Blasiak J, Trzeciak A, Kowalik J. Curcumin damages DNA in human
gastric mucosa cells and lymphocytes. J Environ Pathol Toxicol Oncol
1999;18:2716.
27. Kelly MR, Xu J, Alexander KE, Loo G. Disparate effects of similar
phenolic phytochemicals as inhibitors of oxidative damage to cellular
DNA. Mutat Res 2001;485:30918.
28. Cao J, Jia L, Zhou HM, Liu Y, Zhong LF. Mitochondrial and nuclear
DNA damage induced by curcumin in human hepatoma G2 cells.
Toxicol Sci 2006;91:47683.
29. Urbina-Cano P, Bobadilla-Morales L, Ramirez-Herrera MA, CoronaRivera JR, Mendoza-Magana ML, Troyo-Sanroman R, Corona-Rivera
A. DNA damage in mouse lymphocytes exposed to curcumin and
copper. J Appl Genet 2006;47:37782.
30. Verschoyle RD, Steward WP, Gescher AJ. Putative cancer
chemopreventive agents of dietary origin-how safe are they? Nutr
Cancer 2007;59:15262.
31. NTP Toxicology and Carcinogenesis Studies of Turmeric Oleoresin
(CAS No. 8024-37-1) (Major Component 79%-85% Curcumin, CAS
No. 458-37-7) in F344/N Rats and B6C3F1 Mice (Feed Studies). Natl
Toxicol Program Tech Rep Ser 1993;427:1275.
32. Dance-Barnes ST, Kock ND, Moore JE, Lin EY, Mosley LJ,
DAgostino RB, Jr, McCoy TP, Townsend AJ, Miller MS. Lung
tumor promotion by curcumin. Carcinogenesis 2009;30:101623.
33. Cerutti PA. Prooxidant states and tumor promotion. Science 1985;
227:37581.
34. Klaunig JE, Kamendulis LM. The role of oxidative stress in
carcinogenesis. Annu Rev Pharmacol Toxicol 2004;44:23967.
35. Lopez-Lazaro M. Excessive superoxide anion generation plays a key
role in carcinogenesis. Int J Cancer 2007;120:137880.
36. Lopez-Lazaro M. Dual role of hydrogen peroxide in cancer: possible
relevance to cancer chemoprevention and therapy. Cancer Lett 2007;
252:18.
37. Okamoto M, Kawai K, Reznikoff CA, Oyasu R. Transformation in
vitro of a nontumorigenic rat urothelial cell line by hydrogen
peroxide. Cancer Res 1996;56:464953.
38. Okamoto M, Reddy JK, Oyasu R. Tumorigenic conversion of a
non-tumorigenic rat urothelial cell line by overexpression of
H2O2-generating peroxisomal fatty acyl-CoA oxidase. Int J Cancer
1997;70:71621.
39. Suh YA, Arnold RS, Lassegue B, Shi J, Xu X, Sorescu D, Chung AB,
Griendling KK, Lambeth JD. Cell transformation by the
superoxide-generating oxidase Mox1. Nature 1999;401:7982.
40. Arnold RS, Shi J, Murad E, Whalen AM, Sun CQ, Polavarapu R,
Parthasarathy S, Petros JA, Lambeth JD. Hydrogen peroxide
mediates the cell growth and transformation caused by the mitogenic
oxidase Nox1. Proc Natl Acad Sci USA 2001;98:55505.
41. Szatrowski TP, Nathan CF. Production of large amounts of hydrogen
peroxide by human tumor cells. Cancer Res 1991;51:7948.
42. Burdon RH. Superoxide and hydrogen peroxide in relation to
mammalian cell proliferation. Free Radic Biol Med 1995;18:77594.
43. Aykin-Burns N, Ahmad IM, Zhu Y, Oberley LW, Spitz DR.
Increased levels of superoxide and H2O2 mediate the differential

Letters to the Editor

44.

45.

46.

47.

48.

49.

50.

51.

52.

53.

54.

55.

56.

57.

58.

59.
60.

61.

susceptibility of cancer cells versus normal cells to glucose

deprivation. Biochem J 2009;418:2937.
Church SL, Grant JW, Ridnour LA, Oberley LW, Swanson PE,
Meltzer PS, Trent JM. Increased manganese superoxide dismutase
expression suppresses the malignant phenotype of human melanoma
cells. Proc Natl Acad Sci USA 1993;90:31137.
Zhang Y, Zhao W, Zhang HJ, Domann FE, Oberley LW.
Overexpression of copper zinc superoxide dismutase suppresses
human glioma cell growth. Cancer Res 2002;62:120512.
Safford SE, Oberley TD, Urano M, St Clair DK. Suppression of
brosarcoma metastasis by elevated expression of manganese
superoxide dismutase. Cancer Res 1994;54:42615.
Yan T, Oberley LW, Zhong W, St Clair DK. Manganese-containing
superoxide dismutase overexpression causes phenotypic reversion in
SV40-transformed human lung broblasts. Cancer Res 1996;56:
286471.
Hyoudou K, Nishikawa M, Umeyama Y, Kobayashi Y, Yamashita F,
Hashida M. Inhibition of metastatic tumor growth in mouse lung by
repeated administration of polyethylene glycol-conjugated catalase:
quantitative analysis with rey luciferase-expressing melanoma cells.
Clin Cancer Res 2004;10:768591.
Fang J, Lu J, Holmgren A. Thioredoxin reductase is irreversibly
modied by curcumin: a novel molecular mechanism for its
anticancer activity. J Biol Chem 2005;280:2528490.
McNally SJ, Harrison EM, Ross JA, Garden OJ, Wigmore SJ.
Curcumin induces heme oxygenase 1 through generation of reactive
oxygen species, p38 activation and phosphatase inhibition. Int J Mol
Med 2007;19:16572.
Kang J, Chen J, Shi Y, Jia J, Zhang Y. Curcumin-induced histone
hypoacetylation: the role of reactive oxygen species. Biochem
Pharmacol 2005;69:120513.
Atsumi T, Fujisawa S, Tonosaki K. Relationship between intracellular
ROS production and membrane mobility in curcumin- and
tetrahydrocurcumin-treated human gingival broblasts and human
submandibular gland carcinoma cells. Oral Dis 2005;11:23642.
Sandur SK, Ichikawa H, Pandey MK, Kunnumakkara AB, Sung B,
Sethi G, Aggarwal BB. Role of pro-oxidants and antioxidants in the
anti-inammatory and apoptotic effects of curcumin
(diferuloylmethane). Free Radic Biol Med 2007;43:56880.
Wang H, Mao Y, Chen AY, Zhou N, LaVoie EJ, Liu LF. Stimulation
of topoisomerase II-mediated DNA damage via a mechanism
involving protein thiolation. Biochemistry 2001;40:331623.
Martin-Cordero C, Lopez-Lazaro M, Galvez M, Ayuso MJ.
Curcumin as a DNA topoisomerase II poison. J Enzyme Inhib Med
Chem 2003;18:5059.
Moos PJ, Edes K, Mullally JE, Fitzpatrick FA. Curcumin impairs
tumor suppressor p53 function in colon cancer cells. Carcinogenesis
2004;25:16117.
Tsvetkov P, Asher G, Reiss V, Shaul Y, Sachs L, Lotem J. Inhibition
of NAD(P)H:quinone oxidoreductase 1 activity and induction of p53
degradation by the natural phenolic compound curcumin. Proc Natl
Acad Sci USA 2005;102:553540.
Jiao Y, Wilkinson J, Di X, Wang W, Hatcher H, Kock ND,
DAgostino R, Jr, Knovich MA, Torti FM, Torti SV. Curcumin, a
cancer chemopreventive and chemotherapeutic agent, is a
biologically active iron chelator. Blood 2009;113:4629.
Means RT, Jr. Ironing out complementary medicine. Blood 2009;113:
2701.
Oetari S, Sudibyo M, Commandeur JN, Samhoedi R, Vermeulen NP.
Effects of curcumin on cytochrome P450 and glutathione
S-transferase activities in rat liver. Biochem Pharmacol 1996;51:3945.
Appiah-Opong R, Commandeur JN, Vugt-Lussenburg B, Vermeulen
NP. Inhibition of human recombinant cytochrome P450s by
curcumin and curcumin decomposition products. Toxicology 2007;
235:8391.

C 2009 UICC
Int. J. Cancer: 126, 17711775 (2010) V

Letters to the Editor

Key words: curcumin, toxicity, DNA damage, safety

DOI: 10.1002/ijc.24967
History: Received 31 Jul 2009; Accepted 1 Oct 2009; Online 14 Oct
2009
Correspondence to: Miguel Lopez-Lazaro, Department of
Pharmacology, Faculty of Pharmacy. C/ Professor Garcia Gonzalez,
41012, Sevilla, Spain, Fax: 345-954-23-37-65,
E-mail: mlopezlazaro@us.es

Letters to the Editor

62. Thapliyal R, Maru GB. Inhibition of cytochrome P450 isozymes by

curcumins in vitro and in vivo. Food Chem Toxicol 2001;39:5417.
63. Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far.
Eur J Cancer 2005;41:195568.
64. Goodman GE, Thornquist MD, Balmes J, Cullen MR, Meyskens FL,
Jr, Omenn GS, Valanis B, Williams JH Jr. The beta-carotene and
retinol efcacy trial: incidence of lung cancer and cardiovascular
disease mortality during 6-year follow-up after stopping betacarotene and retinol supplements. J Natl Cancer Inst 2004;96:
174350.

1775

C 2009 UICC
Int. J. Cancer: 126, 17711775 (2010) V