Curcumin Cell Signaling : A Possible Target for Chemotherapy

Current Trends in Biotechnology and Pharmacy, Vol. 2 (2) 226 -238, (2008)
ISSN 0973-8916
Curcumin Cell Signaling: A Possible Target for Chemotherapy
Shahanas Chathoth, Faisal Thayyullathil and Sehamuddin Galadari*
Cell Signaling Laboratory, Department of Biochemistry, Faculty of Medicine and Health Sciences,
UAE University P.O. Box 17666, Al Ain, UAE
* For Correspondence - sehamuddin@uaeu.ac.ae
Abstract
of the enzyme activities which have important
Many components that are derived from role in cell regulation. Curcumin acts as a potent
medicinal or dietary plants, known as inhibitor of Phosphorylase kinase (PhK), and
phytochemicals, posses chemopreventive Phospholipase D (PLD) under in vitro conditions.
properties. Curcumin, the active chemical of the In vivo studies have shown that curcumin inhibits
spice turmeric, exhibits anticancer activity in LPS induced expression of inducible nitric oxide
several cancer cell lines. Nuclear factor kappa B synthase (iNOS), and also acts as a novel
(NF-êB) and activator protein-1 (AP-1) play a inhibitor of class I histone deacetylase (class I
critical role in the transcriptional regulation of HDACs) such as HDAC1, HDAC3, and
genes that have been shown to suppress apoptosis HDAC8. Apart from these, it has been shown
and induce cellular transformation, proliferation, that curcumin induces apoptosis of cancer cells
invasion, metastasis, chemo-resistance, radio- through the generation of the sphingolipid
resistance and inflammation. A number of studies metabolite ceramide. This review attempts to
have shown that curcumin exerts its anti-cancer summarize curcumin cell signaling pathways
effects through the suppression of activation of responsible for cell growth arrest or apoptosis.
NF-êB and AP-1, and lead to the down-regulation
of its target gene products COX-2, cyclin D1,
Key words
Bcl-2, Bcl-xL, cIAP1, xIAP and survivin. On the
Chemoprevention, curcumin, NF-êB,
other hand, Curcumin also is shown to induce apoptosis, ROS, ceramide.
cancer cell growth arrest and apoptosis in several
cell models. Curcumin treatment up-regulates the Introduction
expression of proteins involved in apoptosis and
Cancer cells are characterized by loss of
exhibits common apoptotic features like altered growth control, invasiveness, and metastasis.
expression of Bcl-2 family of proteins, This can be caused by physical, chemical, and
imbalanced mitochondrial trans-membrane biological agents called carcinogens.
permeability (ÄØm), release of cytochrome c,
Smac, and AIF from mitochondria. These effects Carcinogens damage or alter the DNA and lead
induce apoptosis via caspase-dependent and to the transformation of genes controlling cell
independent pathways. There are conflicting proliferation, differentiation, and apoptosis. In
reports as to the role of curcumin in redox normal tissue the rate of normal cell growth and
balance. It has been shown to act as potent death are kept in balance. In cancer this balance
scavenger of reactive oxygen species (ROS), and is disrupted leading to either cellular overgrowth
at the same time it induces free radical generation and/or lack of apoptosis of damaged cells that
and significant cell death through apoptosis in later become malignant. Apoptosis or
other cancer cell models. Both in vivo and in vitro programmed cell death is the mechanism by
studies have shown that curcumin inhibit some which old or damaged cells normally self

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destruct, so induction of apoptosis can be
spice. It has gotten much attention by virtue of
considered as a promising approach towards its great variety of pharmacological activities.
cancer therapy. Indeed, some chemotherapy relies Curcumin exhibits major biological effects such
on apoptosis of tumor cells.
as having anti-inflammatory, antioxidant, and
anti-venom activities. Table 1 summarizes some
Chemotherapy, one of the methods used in of the biological effects of curcumin.
cancer treatment, refers to the approach of Importantly, curcumin has been shown to exhibit
treating cancer cells with anticancer drugs that anti-tumor activities. Several studies support
can destroy cancer cells and stop uncontrolled curcumin as a chemotherapeutic agent as it
cell growth. Research over the last decade has induces cell growth arrest and apoptosis (6-8).
shown that phytochemicals, chemical agents
obtained from some fruits and vegetables, exert Figure 1. Chemical structure of curcumin.
their inhibitory effects on carcinogenesis and
tumor progression. Extensive research in the last
few years have demonstrated that some dietary
components such as curcumin, capsaicin, 6-
gingerol, and ajoene (phytochemicals), which are
present in common spices, have inhibitory effect
on human cancers. This suggests that these Involvement of curcumin in the down-
phytochemicals may serve as chemotherapeutic regulation of anti-apoptotic proteins
agents. In vitro and in vivo experimental studies
indicate that these phytochemicals interfere with
Curcumin down-regulates the expression of
several cell signaling pathways and lead to genes involved in cell growth by inhibiting the
apoptosis and cell cycle arrest. A population based activation of transcription factors involved in cell
study of cancer incidence showed a lower proliferation and survival. It has been shown that
percentage of cancer victims in South East Asian the activation of nuclear factor-kappa B (NF-êB),
countries as they consume large amounts of these an inducible transcription factor, is critical to the
phytochemicals through their diet (1). Since these establishment of cancer. Inactive NF-êB in the
phytochemicals are consumed in daily life as cytoplasm is a heterotrimer composed of three
dietary components, they have received much subunits p50 (NF-êB1), p65 (RelA) and inhibitor
attention among the public and the medical êB (IêBá). Upon stimulation, IêBá is
community. Furthermore, as these agents are phosphorylated by IêB kinase complex (IKK),
obtained from natural sources, and have been followed by ubiquitination-dependent
consumed by people for centuries, they can be degradation of IêBá, leading to nuclear
considered as “safe” chemotherapeutic agents.
translocation, and binding of NF-êB to a specific
Phytochemicals have been shown to inhibit DNA sequence. This results in transcription of
cancer cell growth through the modulation of multiple êB-dependent genes, including TNF-á,
genes that are related to the control of cell IL-6, IL-8 and other chemokines, MHC class II,
proliferation, cell cycle, apoptosis, signal ICAM-1, inducible nitric oxide synthase (iNOS),
transduction, oncogenesis and transcription (2- Cox-2, as well as, apoptosis suppressing proteins
5). Curcumin, or diferuloyl methane (Figure.1), such as Bcl-2 and Bcl-xL which inturn induce
is one of the major components of Curcuma longa cellular transformation, proliferation,
L.(Zingibraceae) and it is used commonly as a differentiation, growth and inflammation.

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Chathoth et al
Table 1. Molecular targets and consequent biological effects of curcumin treatment in different cell
model

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The inhibitory activity of curcumin is not
of NF-êB and Ap-1, and down-regulates the
only restricted to the NF-êB pathway, but also, it
expression of their target gene products, finally
inhibits the pathway of activator protein-1(AP-
leading to cell cycle arrest, suppression of
1), another important transcription factor
proliferation, and induction of apoptosis. These
involved in cell proliferation and survival. AP-1
biological effects are summarized in Figure 2.
consists of a homodimer of c-Jun, or a
heterodimer of c-Jun/c-Fos family members. Like
Inhibition of NF-êB activation upon curcumin
NF-kB, AP-1 regulates the expression of several
treatment
genes that are involved in cell differentiation and
The three NF-êB stimuli; TNF-á, Phorbol
proliferation. Phosphorylation of c-Jun by c-Jun
ester, and Hydrogen peroxide, could not activate
N-terminal kinases (JNKs; also named stress
NF-êB when a human myelomonoblastic
activated protein kinases, SAPKs) is important
leukemia cell, ML-1a, was pre-treated with
for c-Jun transcriptional activity. These kinases
curcumin. Curcumin treatment totally suppressed
(JNK1, JNK2, and JNK3) are members of the
TNF-á induced NF-êB activation, even after
mitogen activated protein kinase (MAPK) family
treating the cells with reducing agents like
that is involved in cellular responses to mitogen
dithiothreitol (DTT) or 2,3-dimercaptopropanol
stimulation, environmental stress,
(DMP). These reducing agents have been shown
proinflammatory cytokines, and apoptotic
to reverse the inhibitory effect of L-1-tosylamido-
stimuli. Besides c-Jun, the JNK pathway also
2-phenylethyl chloromethyl ketone (TPCK) and
activates the transcription factors ATF-2 (9), Elk-
phenylarsineoxide on NF-êB activation (13). The
1 (10), and Sap-1a (11), and interacts with the
effect of curcumin regulation of the IêB/NF-êB
NF-êB pathway (12). Curcumin also has been
pathway in nontransformed intestinal epithelial
shown to inhibit JNK activation. Several studies
cell line IEC-6, human HT-29 colonic epithelial
have shown that curcumin inhibits the activation
cells and Caco-2 epithelial cells, have been
examined by inducing cells with IL-1â. In these
Figure 2. Effect of curcumin on cell survival
studies, it was shown that curcumin down-
pathways; Curcumin inhibits NF-êB activation
regulates IL-1â-mediated ICAM-1 and IL-8 gene
through blocking an upstream signal leading to NIK
expression by inhibiting NF-êB activation,
activity thereby it inhibits phosphorylation of IêBá
through inactivation of IKK, Curcumin inhibits NF-
through blocking an upstream signal leading to
êB activation by inhibiting the activation of IKK
NIK (NF-êB inducing kinase) activity, that
through MEKK1, and Curcumin inhibits AP-1
phosphorylates and activates IêB kinase complex
activation through inhibiting JNK kinase activity.
(14). The critical anti-apoptotic role of NF-êB in
curcumin induced cell regulation is strongly
supported by a study conducted with a relA gene,
encoding the p65 (RelA) subunit of NF-êB, in
transfected L-929 (mouse fibrosarcoma) cells.
The transfected cells showed significant
resistivity to curcumin induced apoptosis when
compared to the parent cell line. On the other
hand, resistivity of the transfected cells was
totally demolished by co-transfection with a
super-repressor form of IêB-á, which is known
to inhibit NF-êB (15).

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Curcumin Cell Signaling
Mantle cell lymphoma (MCL) cell line
PMA induced activation of c-Jun/AP-1 in mouse
JeKo-1, Mino, SP-53, and Granta 519 have been
fibroblast cells NIH 3T3 (20). The transcriptional
used in studying the effect of curcumin in down-
activity of c-Jun is dependent on JNK activation,
regulation of cyclin D1 expression, as these MCL
and is essential for its gene expression (21). Thus,
cells are characterized by overexpression of
inhibition of JNK by curcumin would result in
cyclin D1. Upon curcumin treatment, NF-êB is
inhibition of c-Jun activation, and transcription
inactivated through the inactivation of IêB kinase
of the c-Jun gene. In support of the inhibitory
(IKK) by inhibiting Akt activation. As a
action of curcumin on c-Jun/AP-1 activation,
consequence, curcumin treatment attenuated the
curcumin completely blocks JNK activation by
expression of NF-êB regulated genes such as
various agents such as PMA, ionomycin, ã-
IêBá, cyclin D1, Bcl-2, Bcl-xL and Cox-2.
radiation, UV-C, TNF-á, and sodium
Curcumin treatment also down-regulated the
orthovanadate in Jurkat cells (22). Suppression
expression of NF-êB targeted tumor cell survival
of NF-êB and AP-1 activation upon curcumin
genes cIAP1, xIAP, TRAF1 and survivin leading
treatment is well demonstrated in human
to G1/S arrest, suppression of proliferation, and
promyelotic leukemia (HL-60) cells (23). Phorbol
finally apoptosis (16). A study conducted on the
ester induced activation of NF-êB, AP-1 and its
effect of curcumin on immature B cell lymphoma
DNA binding to its response elements was
cell line (BKS-2) demonstrated curcumin
completely interrupted by curcumin pretreatment.
induced apoptosis through repression of NF-êB
Sustained JNK activity, is found to be pro-
binding activity, and down-regulation of the
apoptotic, whereas, rapid transient JNK
survival genes egr-1, which has been shown to
activation could be anti-apoptotic (24-26). Unlike
be essential for the growth of B lymphoma cells
the inhibitory effect of curcumin on JNK
(17), c-myc, Bcl-xL as well as tumor suppressor
activation, curcumin induced apoptosis in the
gene p53 (2). Ku70, a subunit of Ku protein
human colon cancer cell line HCT166 is
complex, plays a major role in keeping Bax
accompanied by sustained phosphorylation and
protein in an inactive conformation during
activation of JNK and p38 MAPK. Curcumin
apoptosis (18). Overexpression of Ku70 and Bcl-
treatment inhibited NF-êB transcriptional
xL proteins in human colon cancer cell line
activity, but it showed a significant increase in
(SW480) inhibited curcumin induced apoptosis.
This inhibition is achieved through blocking the
AP-1 transcriptional activity (27).
release of cytochrome c, apoptosis inducing
Involvement of curcumin in up-regulation
factor (AIF), and second mitochondria derived
of pro-apoptotic agents
factor of caspase (Smac) from mitochondria,
Curcumin is shown to induce apoptosis in
therefore, inactivating caspase cascade. This
several cancer cell lines through the down-
study supported the role that Ku70 plays in the
regulation of the expression of anti-apoptotic
retention of Bax in the cytosol (19).
proteins. However, curcumin treatment up-
Inhibition of AP-1 and JNK activation regulates the expression of proteins involved in
upon curcumin treatment
apoptosis and exhibits common apoptotic
Activator protein-1 has a central role in
features like altered expression of Bcl-2 family
controlling the eukaryotic gene expression.
of proteins, imbalanced mitochondrial trans-
Activation of c-Jun/AP-1 plays an important role
membrane permeability (ÄØm), release of
in signal transduction of phorbol 12-myristate
cytochrome c, Smac, and AIF from mitochondria
13-acetate (PMA) induced tumor promotion. It
which in turn induce apoptosis via caspase-
has been reported that curcumin can suppress the
dependent and independent pathways (Figure 3).

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Curcumin also facilitates the rapid generation of
treated with curcumin. In this case curcumin
ROS that leads to cell death in several cancer
induced apoptosis at G2 phase of MCF-7 cells,
cell lines.
while it blocked NME cell cycle progression
Figure 3. Schematic representation of curcumin
without apoptosis. Curcumin induces apoptosis
induced apoptotic signaling pathways. Curcumin
in carcinoma cells through increased expression
induces apoptosis through ROS generation,
of p21Waf-1, a cell cycle inhibitory protein, p53,
cytochrome c release, activation of caspase
and cytochrome c release (30). Curcumin has
cascade, PARP cleavage and DNA
been shown to arrest cell cycle progression, and
fragmentation. Curcumin induces rapid
induce apoptosis in vascular smooth muscle cell
generation of ceramide which also leads to
line A7r5 through reduced expression of c-myc,
apoptosis. The doted arrows indicate not well-
and Bcl-2, without altering p53 expression level
established pathways.
(31). Curcumin posses chemopreventive
potentials against a panel of acute lymphoblastic
leukemia cells (T-ALL) including CEM, HSB2,
Jurkat and Molt-4 cells by inducing apoptosis. It
has been demonstrated that curcumin suppresses
targets of PI3'-kinase i.e. Akt, FOXO, and
GSK3â, and it induces caspase-dependent
apoptosis through cytochrome c release,
activation of caspase-3 and PARP cleavage. At
the same time, curcumin down regulates the
expression of survival proteins such as cIAP,
xIAP and survivin (32). Curcumin treatment
effectively suppressed the AK-5 (a rat histiocytic
tumor) development in an in vivo study. In vitro
Involvement of p53 and caspase cascade study with single AK-5 tumor cell BC-8
in curcumin induced apoptosis
exhibited apoptosis through ROS generation,
The inhibitory action of curcumin on colon
caspase-3 activation, but not caspase-1, PARP
adenocarcinoma was has been proven by treating
cleavage, and DNA fragmentation (8). It has been
the human HT-29 colon adenocarcinoma cell line
reported that p53 is not necessary for intercellular
with curcumin. These undergo apoptosis by
induction of apoptosis (33), and the relationship
activating p53 through phosphorylation at Ser15
between p53 and c-myc in the process of
residue, and by decreased expression of the anti-
apoptosis is still controversial (34,35). Curcumin
apoptotic protein Bcl-2, increased expression of
has been reported to induce apoptosis in p53
pro-apoptotic protein Bax, and increased
proficient A549 and p53 deficient H1299 human
caspase-3 and caspase-9 activation (28).
lung cancer cell lines. In both cell lines curcumin
Similarly, curcumin induced apoptosis in the
induces apoptosis by up-regulation of c-myc, and
human breast cancer cell line MCF-7 by
potentiating p53 DNA binding activity which
down regulation of anti-apoptotic genes BclXL
induces Bax expression (29). Another interesting
and Bcl-2. This result suggests a multiple p53
result was obtained when MCF-7 cells and
independent pathways in lung cancer cells where
normal mammary epithelial cells (NME) were
c-myc is possibly playing a major role (36).

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Chathoth et al
Involvement of reactive oxygen species in Inhibition of enzymatic activity by
curcumin induced apoptosis
curcumin
Being an antioxidant, anti-inflammatory
Several studies have shown that curcumin and anti-carcinogenic agent, curcumin has been
acts as an anti-oxidant, and as a potent scavenger shown to inhibit some enzyme activities that have
of free radicals, thereby, usually being considered important roles in cell regulation. Some of the in
as protecting cells from oxidative stress. vitro experimental studies have shown that
Curcumin acts as a potent scavenger of a variety curcumin directly acts as a potent inhibitor of
of reactive oxygen species (ROS) including certain enzymes. It has been reported that
superoxide anion (37), hydroxyl radical, singlet curcumin inhibits the activity of different protein
oxygen (38), and nitric oxide radicals (39). On kinases such as protein kinase A (PKA), protein
the other hand, curcumin has been shown to kinase C (PKC), cytosolic protamine kinase
induce free radical generation and significant cell (cPK), phosphorylase kinase (PhK),
death through apoptosis under certain autophosphorylation-activated protein kinase
experimental conditions. There are conflicting (AK), and pp60c-src tyrosine kinase. Among these
reports as to the role of curcumin in redox kinases, curcumin acted as a selective and potent
balance. An investigation aimed at finding out inhibitor of PhK (45). The effect of curcumin has
been tested on the enzyme activities of
the role of curcumin as an antioxidant against phospholipases such as ARF/GTPãS-dependent
the oxidative stress damage induced by H O on
2
2
phospholipase D (PLD), phosphatidylinositol
the neuronal cell NG108-15 leads to a specific phospholipase C, phosphatidylcholine-
contradictory result. Co-treatment of curcumin phospholipase C, phospholipase A2 and
with H O increased cell viability of NG108-15
2
2
sphingomyelinase in a cell free system. Curcumin
cells, but when curcumin was pretreated, not only inhibited enzyme activities of all phospholipases
curcumin was unable to inhibit H O induced cell
2
2
except sphingomyelinase. Amongst these, PLD
death, it actually significantly decreased cell was effectively inhibited at lower concentration
viability (40). The role of ROS generation in of curcumin, which was further confirmed in
curcumin induced apoptosis or necrosis is well intact mouse macrophage J774.1 cell model by
studied using the human osteoblast cell line inducing the cells with TPA (46).
HFOb1.19. Low concentration of curcumin
Apart from its in vitro inhibitory action,
treatment leads to increased ROS generation, curcumin has been shown to inhibit some of the
JNK activation, loss of ÄØm, caspase-3 enzyme activities in vivo by interfering with their
activation, PARP cleavage and finally to gene expression level. Curcumin inhibited
apoptosis. Whereas, high dose treatment led to P185neu
autophosphorylation and
less ROS generation, loss of ÄØm and necrosis, transphosphorylation by inhibiting P185neu
while, JNK and caspase-3 had no effect. tyrosine kinase, a potent oncoprotein that is
Moreover, intracellular ATP levels, important overexpressed in breast cancers, under in vitro
mediators capable of switching the mode of cell condition and completely depleted the protein in
death from apoptosis to necrosis (41), play a vivo and suppressed the growth of breast cancer
major role in switching the mechanism of cell cell line AU-565 (47). An inhibitory effect of
death from apoptosis to necrosis (42). Apart from curcumin on nitric oxide synthase (NOS) was
these, several studies have reported that curcumin observed when murine macrophage RAW 264.7
induces apoptosis through ROS generation cells were treated with curcumin and its
(43,44).
hydrogenated metabolites tetrahydrocurcumin,

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hexahydrocurcumin, and octahydrocurcumin.
cause ceramide accumulation before committing
Lipopolysaccharide (LPS) has been shown to
to apoptosis. Ceramide is cleaved to sphingosine
induce the expression of iNOS by the activation
and free fatty acid by ceramidase enzymes,
NF-êB (48). Only curcumin completely
sphingosine is further metabolized by
suppressed the expression of iNOS mRNA level
phosphorylation to sphingosine-1-phosphate by
when macrophages were induced with LPS (49).
sphingosine kinase. Ceramidases are emerging
Apart from these, curcumin has been shown to
as a key enzyme activity, as they play an
act as a novel inhibitor of class I histone
important role in the regulation of the levels of
deacetylase (class I HDACs) such as HDAC1,
ceramide, sphingosine, and sphingosine-1-
HDAC3, and HDAC8. Evidence suggests that a
phosphate and consequently these sphingolipid
family of histone deacetylases may exist in order
metabolite mediated biology.
to regulate diverse cellular functions, including
chromatin structure, gene expression, cell cycle
Ceramide is generated via two main
progression, and oncogenesis (50). A curcumin
pathways; the de novo pathway, through the
induction study conducted on the Burkkit
condensation of serine and palmitoyl CoA, and
lymphoma cell line Raji, has shown that curcumin
sphingomyelinase pathway, through the cleavage
induced apoptosis by inhibiting the histone
of sphingomyelin to ceramide and
deacetylase enzymes HDAC1, HDAC3 and
phospatydilcholine. Capsaicin, another well
HDAC8 and up-regulating the expression of Ac-
studied phytochemical obtained from red chili
histone H4 (51). Telomerase, a reverse
pepper, induces apoptosis through ceramide
transcriptase enzyme highly expressed in tumor
generation via sphingomyelin hydrolysis (53).
cells, activity was suppressed by curcumin and
Recently, it has been demonstrated that curcumin
induced apoptosis in human chronic myelogenic
treatment leads to significant generation of
leukemia (K-562) cells. The mode of curcumin
ceramide through the de novo pathway and
inhibition of the enzyme activity was due to the
apoptosis in the colon cancer cell line HCT116.
suppression of translocation of telomerase reverse
When these cells are pre-treated with myriosin,
transcriptase (TERT) from cytosol to nucleus
a specific inhibitor of the de novo pathway, it
(52).
attenuated curcumin induced ceramide
generation, and markedly reduced cell death
Curcumin induces sphingolipid mediated cell
(54). The above mentioned evidence are
signaling
indicative of possible roles for important
Sphingolipids have recently emerged as
sphingolipid metabolites in curcumin mediated
important bioactive molecules in cell regulation.
cell regulation. Its mechanism of action remains
They have important biological roles in cell stress
incompletely understood and further
responses, cell growth, apoptosis, angiogenesis,
investigations are needed to understand the
differentiation, and senescence. The sphingolipid
biological role of sphingolipids in curcumin
metabolites ceramide, sphingosine, and
sphingosine-1-phosphate have been shown to
mediated cell death.
take an important part in the regulation of cell
function. Intracellular ceramide and sphingosine
Conclusion
levels are associated with growth arrest and
Our review attempts to appraise the
apoptosis, whereas, sphingosine-1-phospate is
molecular mechanisms of phytochemical action
associated with suppression of apoptosis. In vitro
on cells. Most of the phytochemicals have been
studies of many stimuli such as heat, UV, ã-
shown to induce cell growth arrest or apoptosis
radiation, TNF-á, and chemotherapeutic agents
and thereby they act as chemopreventive agents.

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234
Curcumin Cell Signaling
Among these curcumin holds its prime position 4.
Lee, S.H., Cekanova, M. and Baek, S.J.
as it has been well studied and shown to induce
(2007). Multiple mechanisms are involved
cell growth arrest or apoptosis in a variety of
in 6-gingerol-induced cell growth arrest
malignant cell lines. Curcumin can be considered
and apoptosis in human colorectal cancer
as a chemopreventive agent that can be
cells. Molecular Carcinogenesis, 47: 197-
developed as an anti-cancer drug. Complete
208.
removal of cancer without damage to the rest of
the body is the goal of chemotherapy. The 5.
Li, M., Ciu, J.R., Ye, Y., Min, J.M., Zhang,
effectiveness of chemotherapy by using chemical
L.H., Wang, K., Gares, M., Cros, J.,
drugs is often limited by cytotoxicity to the other
Wright, M. and Leung-Track, J. (2002).
tissues in the body. However, being consumed
Antitumor activity of Z-ajoene, a natural
compound purified from garlic: antimitotic
as dietary supplements for many centuries,
and microtubule-interaction properties.
curcumin can be considered as the safest
Carcinogenesis, 23: 573-579.
chemical agent for chemotherapy. More
biological and clinical investigations are needed 6.
Kawamori, T., Lubet, R., Steele, V.E.,
to establish this phytochemical as an anti-cancer
Kelloff, G.J., Kaskey, R.B., Rao, C.V. and
drug.
Reddy, B.S. (1999). Chemopreventive
Acknowledgment: Research work at the Cell
effect of curcumin, a naturally occurring
Signaling Laboratory is financially supported by
anti-Inflammatory agent, during the
grants from The Terry Fox Foundation for Can-
promotion/progression stages of colon
cer Research (UAE-05-98), The Sheikh Hamdan
cancer. Cancer Research, 59: 597-601.
Award for Medical Sciences, and grants from the 7.
Odot, J., Albert, P., Carlier, A., Tarpin, M.,
Faculty of Medicine and Health Sciences, United
Devy, J. and Madoulet, C. (2004). In vitro
Arab Emirates University.
and in vivo anti-tumoral effect of curcumin
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