CURCUMIN INDUCED CELL DEATH AND INHIBITION OF TELOMERASE ACTIVITY IN MOUSE LYMPHOMA P388D1 CELLS

EXCLI Journal 2009;8:20-29 – ISSN 1611-2156
Received: August 09, 2008, accepted: January 18, 2009, published: January 21, 2009

Original article:

CURCUMIN INDUCED CELL DEATH AND INHIBITION OF
TELOMERASE ACTIVITY IN MOUSE LYMPHOMA P388D1 CELLS

Vijendra Kumar Mishra1*, Ashok Kumar1

1 Microbial Biotechnology Unit, School of Biotechnology, Faculty of Science, Banaras Hindu
University, Varanasi-221005, (U.P); India.
* Corresponding author: Vijendra Kumar Mishra. E-mail: mishravijendra@yahoo.co.in. Tele-
phone No: +91-542-309015; Fax No: +91-542-303686

ABSTRACT

Telomerase, a potential marker for tumorigenesis, has been found to be activated in more than
85-90% of human cancer. Curcumin is the major biologically active, yellow phytochemical
compound of Curcuma longa (Zingiberaceae). The present study is aimed to investigate the
capacity of curcumin on the regulation of telomerase activity and induction of apoptosis in
P388D1 mouse lymphoma cells. Here, we demonstrate that curcumin at a concentration of 3.5
µM and an incubation period of 48h induces apoptosis and inhibits telomerase activity in the
P388D1 cells. Curcumin induced apoptosis and telomerase activity in P388D1 lymphoma
cells was confirmed by enumeration of apoptotic cells, % DNA fragmentation and RT-PCR.
The culture supernatant of lymphoma cells treated with curcumin showed a higher level of
nitric oxide content. RT-PCR analysis revealed over expression of TNF-? and IL-1? and inhi-
bition of the antiapoptotic Bcl-2 and human catalytic subunit hTERT in the curcumin treated
lymphoma cells as compared to untreated cells. Taken together the result shows that curcumin
could significantly inhibit tumor proliferation and induce apoptosis in lymphoma cells. Thus,
curcumin should be further tested as a possible antineoplastic agent.

Keywords: curcumin, apoptosis, RT PCR, lymphoma


INTRODUCTION

Curcumin (diferuloylmethane), a poly-

phenolic compound (molecular formula
Figure 1: The structure of curcumin
C21H20O6 ) isolated from the plant Curcuma

longa, has been widely used as a spice and
Recently, curcumin has gained special in-
coloring agent (Araÿjo and Leon, 2001;
terest due to its curative impact on numer-
Goel et al., 2008). Curcumin (Figure 1) acts
ous ailments such as wound healing, diabe-
as potent antioxidant, anti-inflammatory
tes, Alzheimer disease, Parkinson disease,
and antiproliferative therapeutic agent
cardiovascular disease, pulmonary disease
(Jagetia and Aggarwal, 2007; Alaikov et al.,
and arthritis (Goel et al., 2008). Curcumin
2007). Commercially, curcumin contains
can act as a potent immunomodulatory
approximately 77
% diferuloylmethane,
agent that can modulate the activation of
17 % demethoxycurcumin, and 6 % bisde-
T cells, B cells, macrophages, neutrophils,
methoxycurcumin (Goel et al., 2008).
natural killer cells, and dendritic cells (Gau-
risankar and Das, 2008; Jagetia and Aggar-
wal, 2007). Several reports have docu-
20

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EXCLI Journal 2009;8:20-29 – ISSN 1611-2156
Received: August 09, 2008, accepted: January 18, 2009, published: January 21, 2009

mented that curcumin can induce apoptosis
phenomena (Watanabe 2001; Mukherjee et
in cancer cells from liver, colon, breast,
al., 2007). Telomerase is thus proving to be
stomach and duodenal tissue (Shi et al.,
a reliable marker for the proliferating ca-
2006).
pacity and tumor mass of cancer patients
Reports suggest apoptosis involves
(Watanabe 2001; Gao and Chen, 2007).
changes in the expression of apoptotic
This makes telomerase a good target for
agent’s like Bcl-2, TNF-? and IL-1B ap-
cancer diagnosis. The present work was un-
pears to be a critical determinant of a cells
dertaken to investigate the underlying
threshold for undergoing apoptosis (Anand
mechanism involved in induction of apop-
et al., 2008). Curcumin has been shown to
tosis and chemoprevention by curcumin in
downregulate the expression of various pro-
P388D1 cells.
inflammatory cytokines including TNF-?

and interleukin-1, through inactivation of
MATERIALS AND METHODS
the transcription factor NF-?B (Jagetia and
Aggarwal, 2007). Thus, TNF-? and IL-1?
Cell lines and treatment with curcumin
could be identified as the therapeutic targets
P388D1 mouse lymphoma cells were
in cancer therapy. Extensive research work
obtained from the National Centre for Cell
suggest that curcumin acts as a potent scav-
Science, Pune, India. Cells were cultured in
enger of a variety of reactive oxygen spe-
DMEM culture medium, supplemented
cies (ROS) including superoxide anion
with 4 mM L-glutamine containing 10 %
(Khar et al., 2001), hydroxyl radical, singlet
fetal bovine serum, penicillin (100 IU/ml)
oxygen (Subramanian et al., 1994), and ni-
and streptomycin (100 mg/ml) at 37 0C with
tric oxide radicals (Sreejayan and Rao,
5 % CO2 in air. Before each experiment,
1997) that leads to apoptosis in several can-
cells were passaged three times. Curcumin
cer cell lines (Woo et al., 2003; Anand et
was dissolved in dimethyl sulfoxide
al., 2008).
(DMSO) and diluted further in water.
Telomere is a repeating (5’-TTAGGG-
P388D1 cells were treated with curcumin at
3’), non-coding DNA sequence located at
a final concentration of 3.5 µM for 48 h.
terminal ends of the chromosomes (Moyzis
Cells cultured in media containing an
et al., 1988). Telomere is regulated by an
equivalent concentration of DMSO and
enzyme namely telomerase, a ribonucleo-
without curcumin served as a control.
protein, with the function of a DNA poly-

merase. The telomerase holoenzyme con-
Morphological evaluation of apoptotic
sists of the catalytic subunit reverse tran-
cells
scriptase protein hTERT (Nakamura et al.,
Percentage of apoptotic cells were
1997), the telomerase RNA template sub-
measured using standard protocol of Kerr et
unit, hTR, that provides a template r-5’-
al. (1972), where apoptotic cells were
CUAACCCUAAC-3’ (Feng et al., 1995)
stained with Wright’s staining. After cur-
and other associated proteins (Harrington et
cumin treatment, cells were removed from
al., 1997). A strong correlation has been
the culture plate using Trypsin/EGTA. A
shown between TERT mRNA expression
drop of cell suspension after air drying was
and telomerase activity in a variety of can-
fixed in methanol and stained with Wright’s
cer cells such as breast, colon, gallbladder,
solution, and then mounted in a permanent
lung, stomach and oesophagus (Jagetia and
medium and analyzed. Apoptotic cells were
Aggarwal, 2007; Alaikov et al., 2007; Goel
identified on the basis of morphological
et al., 2008; Salvioli et al., 2007). Reports
features that included, contracted cell bod-
suggest that human telomerase subunit
ies, condensed uniformly circumscribed and
hTERT overwhelmingly activated in 80 %
densely stained chromatin or membrane
human cancer cells, which prevents te-
bound apoptotic bodies containing one or
lomere shortening and activate apoptotic
more nuclear fragments.
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EXCLI Journal 2009;8:20-29 – ISSN 1611-2156
Received: August 09, 2008, accepted: January 18, 2009, published: January 21, 2009

Agarose gel electrophoresis of DNA
10 ml glacial acetic acid, 150 µl concen-
Extraction of DNA from P388D1 lym-
trated H2SO4 and 50 µl of acetaldehyde so-
phoma was performed following the
lution] were added and the samples were
method given by Pringent et al. (1993) with
allowed to stand overnight at room tem-
some modifications. Cell suspension was
perature to develop colour. 100 µl of the
washed in PBS and lysed in 0.5 ml of lysis
resulting coloured solution was transferred
buffer containing mM Tris HCl, 75 mM
to a 96-well, flat-bottomed ELISA plate and
NaCl 10
mM EDTA, 0.5
% SDS and
optical density was measured at 600 nm in a
0.15 mg/ml proteinase K and incubated for
microtiter plate reader. The percentage of
4 h at 50 0C. Lysates were spun down at
DNA fragmentation was calculated as:
10,000xg for 20 min at 4 0C. The super-
% DNA fragmentation= [T/ (T+B)] x 100.
natant was collected carefully and a solu-
Samples were carried out in duplicate. Blue
tion of 0.5 M NaCl and 50 % absolute etha-
colour was developed in both treated and
nol was added to precipitate DNA. The pre-
untreated samples.
cipitated DNA was resolubilized in 30 µl

TE buffer (10 mM Tris HCl and 1 mM
Assay for NO production
EDTA, pH 8.0) for 1h at 60 0C and then
The nitrite concentration in medium
10 µl of loading dye (bromophenol blue
was measured following according to
0.025 %, xylene cyanol and 30 % glycerol
Srivastava et al. (2004). Briefly, 100 µl of
in water) was added. 40 µl of the sample
cell-free culture supernatants were collected
was loaded into the well of 1.5 % agarose
from each well of the 96-well microplates.
gel and electrophoresed in the presence of
An equal volume of Griess reagent (one
0.5 µg/ml ethidium bromide. After the run,
part 1 % sulfanilamide in 2.5 % H3PO4 plus
DNA was visualized and photographed on a
one part 0.1 % naphthylethylenediamine
UV transilluminator.
dihydrochloride in distilled water) was

added and the mixture incubated for 10 min
DNA fragmentation assay
at room temperature. The absorbance at
A quantitative determination of DNA
540 nm was measured with an automatic
fragmentation was carried out according to
microplate reader. Nitrite concentrations
the method of Sellins and Cohen (1987),
were calculated using sodium nitrite as a
with minor modifications. Cells (1 x 106
standard. Data were expressed as µM ni-
cells/ml) were lysed in 0.5 ml Tris-EDTA
trite/1.5 x105 cells originally plated. In all
buffer, pH 7.4, containing 0.2 % (v/v) Tri-
experiments nitrite contents in wells con-
ton X-100 and the fragmented DNA was
taining medium without cells were also
separated from intact chromatin in a micro-
measured and subtracted from the values in
fuge tube (labelled as A) by centrifugation
the presence of cells. Samples were carried
at 13,000 g at 4 0C for 10 min. Supernatant
out in triplicate. Pink colour was developed
containing fragmented DNA was trans-
in both treated and untreated samples. The
ferred to second microfuge tube (labelled as
amount produced was expressed as
T). 25 % TCA (0.5 ml) was added to each
1x10-7 mM.
T
and B
tube and vortexed vigorously.
DNA was precipitated overnight at 4 0C and
Isolation of RNA
pelleted by centrifugation at 13,000 g at
Total cellular RNA was extracted from
4 0C for 10 min. Supernatants were dis-
P388D1 cells using GeNei Total RNA ex-
carded and 80 µl of 5 % TCA was added to
traction Kit according to the manufacturer's
each pellet. DNA was hydrolyzed by heat-
instructions. Samples were resuspended in
ing at 90 0C for 15 min. At this stage, a
RNase-free water. RNA was quantified
blank was included containing 80 µl of 5 %
from the absorbance recorded at an optical
TCA. A 160 µl aliquot of freshly prepared
density of 260 nm (Jenway, Essex, UK).
DPA reagent [150 mg diphenylamine in

22

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EXCLI Journal 2009;8:20-29 – ISSN 1611-2156
Received: August 09, 2008, accepted: January 18, 2009, published: January 21, 2009

RT-PCR analysis of hTERT, hTR, Bcl-2,
prevent PCR carry over contamination, in-
IL-1? and TNF-?
cluding physical separation of the reaction
The resulting RNA was subjected to
area from the analysis area. Each RT-PCR
single step RT-PCR using the GeNei one
was repeated twice and representative re-
step RT-PCR Kit; according to the manu-
sults are shown. Housekeeping genes ?-
facturer's instructions. Briefly, 3 µg RNase-
actin was used as internal control for equal
free RNA template was subjected to RT-
loading.
PCR amplification in a final volume of

25 µl. The template RNA used for amplifi-
Statistical analysis
cation was denatured at 65 0C for 5 min,
All statistics were carried out using
followed by heating at 55 0C for 45 min for
SPSS software. Values were expressed as
initial cDNA preparation in the presence of
mean ± SD. Group means are compared
reverse transcriptase. The primer sets used
using the unpaired student's t-test. A prob-
for each gene of interest were as follows:
ability value of 0.05 or less was considered
Bcl-2: 5`-primers: 5`-
significant.
GAACACCAGAATCAAGTGTTCG-3` and 5`-

CAGGTGGACCACAGGTGGC-3`, size of ampli-
cons: 455 bp; TNF-?, 5`-primer: 5`-
RESULTS
ATGAGCACTGAAAGCATGATCCGG-3` and
5`GCAATGATCCCAAAGTAGACCTGC-3`, ‘size
Curcumin induced apoptosis of P388D1
of amplicons: 695 bp; IL-1?, 5`-primer: 5`-
cells
ATGGCAGAAGTACCTAAGCTCGC-3` and 5`-
Cells treated with curcumin and subse-
CACAAATTGCATGGTGAAGTCAG-3`, size of
quently visualised with Wright’s stain and
amplicon: 802 bp; ?-Actin 5`- primer: 5`-
GGGTCAGAAGGATTCCTATG-3` and 5`-
examined under phase contrast microscope
CTAGAAGCATTTGCGGTGGAC-3`, size of am-
showed characteristic apoptotic features,
plicons: 1000 bp; hTERT, 5`-primer: 5`-
such as chromatin condensation and nuclear
CGGAAGAGTGTCTGGAGCAA-3` and 3`- fragmentation (Figure 2).
primer: 5`-GGATGAAGCGGAGTCTGGA-3`, size

of amplicons: 145 bp; for hTR, 5`- primers 5`-
GGGTTGCGGAGGGTGGGCCT-3` and 3`- prim-
ers 5`-ACGGGCCAGCAGCTGACAT-3`, size of
the amplicon 185 bp.
The reaction master mix was prepared ac-
cording to the manufacturer’s protocol. The
primer (Met. Int. AG, Deutschland, Ger-
many) concentration was 20 pmol for each
set. Thermal programme was kept similar
for all amplifications. The gene amplifica-
tions were performed with an initial incuba-
tion step at 94 °C for 3 min, followed by
31 cycles at 94 °C for 60 seconds, 60 0C for
1 min (Bcl-2: 58 0C for 1 min and hTERT:

57 0C for 1 min) and 72 °C for 1.5 min with
Figure 2: Lymphoma cell undergoes apoptosis
a final extension at 72 °C for 10 min. PCR
after treatment with 3.5 µM of curcumin for
48 h, shows chromatin condensation, nuclear
products were separated by electrophoresis
fragmentation, presence of apoptotic bodies
on a 2 % agarose gel containing ethidium
and surface blabbing in an apoptotic cell.
bromide and DNA bands were detected in
gel documentation unit (Bio-Rad Laborato-
Other morphological features of apop-
ries, Hercules, CA, USA). The intensity of
tosis such as cell shrinkage and presence of
the bands corresponding to Bcl-2, TNF-?
apoptotic bodies were also evident. One
and IL-1B and ?-actin were calculated using
hundred cells were scored at randomly and
Quantiscan software. Due care was taken to
classified into apoptotic and non apoptotic
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EXCLI Journal 2009;8:20-29 – ISSN 1611-2156
Received: August 09, 2008, accepted: January 18, 2009, published: January 21, 2009

cells based on above characteristics. Per-
DNA ladder profile
centage of apoptotic cells was increased by
To further examine the effect of curcu-
nearly 2 fold, as shown in Figure 3.
min on agarose gel electrophoresis on tu-
mor cells at 3.5 µM concentration for 48 h.
Fragmented DNA ladders were observed in
70
curcumin treated tumor P388d1 cells as rep-
60
resented in Figure 5. No significant frag-
l
l
mentation were observed in the untreated
50
e

C
tumor cells (reference control).
c
ti 40

to
p
o 30

Ap 20
%
C
T.
10
Figure 5: Agarose
gel electrophoresis
0
profile of P388D1
Control
Treated
cells at 3.5
µM
curcumin for 48 h.
Figure 3: Percent of apoptotic P388D1 cells
C indicate un-
observed under phase contrast microscope af-
treated and T for
ter treatment with 3.5 µM of curcumin for 48 h.
treated cells.
Values represented mean ± S.D. (n=100)
% DNA fragmentation assay
To examine further the apoptotic char-
acteristics in curcumin-treated lymphoma
cells, the % DNA fragmentation was de-
termined. Induction of apoptosis was evi-
dent (Figure 4), whereby the % DNA frag-
mentation was increased by more than 2-
fold in curcumin-treated cells compared to
control cells.


70


n 60
NO production analysis
t
i
o
t
a
Curcumin treated and untreated culture
n 50
supernatants of tumor cells, incubated in
me 40
DMEM medium were analyzed for NO
g
r
a
content. Culture supernatant of curcumin
f 30
A
treated tumor cells showed higher level of
N 20
NO content compared to untreated tumor
%D
cells. The NO content is shown in Figure 6,
10
which demonstrates stimulation of NO pro-
0
duction in the curcumin treated lymphoma
Control
Treated
cells as compared to untreated cells.
Figure 4: Percent of DNA fragmented P388D1

cells after treatment with 3.5 µM of curcumin for
48 h.

24

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EXCLI Journal 2009;8:20-29 – ISSN 1611-2156
Received: August 09, 2008, accepted: January 18, 2009, published: January 21, 2009

6
5
l
l
s
)

ce
4
6
/
10
3
M
µ
(
2
i
t
r
i
t
e
(
N
1
0

Control
Treated

Figures 7-10: RT–PCR analysis of TNF-?, IL-
1?, ?-actin and Bcl-2 gene expression after
Figure 6: Nitric oxide produced by P388D1
treatment with 3.5 µM curcumin for 48 h, re-
cells after treatment with 3.5 µM of curcumin for
spectively. Where lane: C represents P388D1
48 h.
cells without curcumin treatment and T repre-
sents with Curcumin treatment.
RT-PCR expression analysis of Bcl-2, IL-

1? and TNF-?

To explore the possible mechanism by
RT PCR expression analysis of hTERT
which curcumin induced apoptosis in
and hTR
P388D1 cells, the expression of both pro-
To assess the effects of curcumin on te-
and anti-apoptotic mRNA was analyzed by
lomerase activity, P388D1 cells were
RT PCR analysis. Changes in the mRNA
treated with 3.5 µM of curcumin for 48 h.
expression levels of Bcl-2, TNF-? and IL-
Telomerase activity was analyzed by RT-
1B in P388D1 cells were measured, to ex-
PCR profile of human telomerase catalytic
amine their possible contribution to the
subunit (hTERT) and RNA subunit of the
mechanism of curcumin-induced apoptosis.
human telomerase complex (hTR). Results
RT-PCR analysis revealed that mRNA lev-
are represented in Figures 11-13. Compared
els of TNF-? and IL-1B (Figures 7 and 8)
to untreated cells, the telomerase activity of
increased with a concomitant decrease in
P388D1 cells was significantly suppressed.
Bcl-2 mRNA (Figure 10). No significant
Percentage inhibition of telomerase was
changes were observed in the levels of ?-
calculated from band intensity. Intensity
actin mRNA (reference control) (Figure 9).
obtained from untreated cells was consid-
The expression level of Bcl-2 was de-
ered to have 100 % telomerase activity and
creased to 60 % of control levels at 3.5 µM
accordingly intensities were calculated for
of curcumin. By contrast, TNF-? and IL-1B
the treated cells. Results revealed that the
levels were increased to 2 to 3 fold higher
telomerase activity was inhibited to the ex-
than control levels, at the same concentra-
tent of 25 % and 40 % after 48 h treatment
tion of curcumin.
with 3.5 µM curcumin, respectively. Ex-

pression levels were calculated from the
intensities obtained in two to three inde-
pendent experiments.
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EXCLI Journal 2009;8:20-29 – ISSN 1611-2156
Received: August 09, 2008, accepted: January 18, 2009, published: January 21, 2009

chrome c is involved in the activation of
caspases and thus initiates the apoptotic
pathway (Khar et al., 2001). It has been
suggested that low dose of curcumin treat-
ment leads to increased ROS generation in
comparison to higher doses (Chan et al.,
2006). Furthermore, the release of cyto-
chrome c leads to inhibition of the mito-
chondrial respiratory chain, that could be
Figures 11-13: RT–PCR analysis of hTERT,
assumed to the overproduction of ROS
hTR and ?-actin expression after treatment with
(Schulze-Osthoff et al., 1992). Studies
3.5 µM curcumin for 48 h, respectively, where
demonstrated depletion of endogenous anti-
lane C represents P388D1 cells without curcu-
oxidant level or increase of ROS led induc-
min treatment and T represents with Curcumin
treatment.
tion of programmed cell death in various

tumor cells (Buttke and Sandstrom, 1994).
DISCUSSION
Therefore, curcumin induced generation of

antioxidant associated with apoptosis at
Over the last decade, a significant re-
3.5 µM in P388D1 lymphoma/ leukemia
search interest has been generated around
cells could not be ignored.
curcumin, the major constitutes of turmeric,
In vitro investigations have demon-
because of its anti-inflammatory and anti-
strated that Bcl-2 acts as a malignant factor
neoplastic properties (D'Incalci et al.,
causing various types of carcinoma, in-
2005). However, hardly any study has been
cludes lung cancer and breast cancer (Ichi-
reported to date regarding effect of low
kawa et al., 2004). On the other hand TNF-
dose of curcumin on induction of apoptosis
? and IL-1? are the key mediator of apop-
via inhibited of telomerase activity and ac-
totic pathway, tumor proliferation and dif-
cumulated reactive oxygen species. In the
ferentiation (Mandal and Kumar, 1997).
present study, we focused on the effect of
Studies suggest IL-1? acts synergistically
curcumin on telomerase activity to clarify
with TNF-?, activates proinflammatory re-
the anti-proliferating effect of curcumin in
sponses in a wide range of tumor cells
P388D1 cells derived from mouse lym-
(Goel et al., 2008; Cho et al., 2007). Studies
phoma/leukemia cells. Recent studies have
demonstrated the expression of the catalytic
indicated that inhibition of tumor cell
subunit TERT correlates with telomerase
growth is associated with the promotion of
activity during cellular differentiation and
apoptosis and decrease in telomerase ex-
neoplastic transformation. Moreover, cur-
pression (Cui et al., 2006; Chakraborty et
cumin mediated downregulation of telom-
al., 2006) in a dose dependent manner
erase activity is due to the inhibition of
(Mukherjee et al., 2007). Moreover, dose
translocation of telomerase reverse tran-
dependent cytotoxic effect of curcumin in
scriptase (TERT) from cytosol to nucleus
induction of apoptosis in various cells has
(Chakraborty et al., 2006). The present
been well documented (Alaikov et al.,
finding illustrates that suppression of tumor
2007). Curcumin mediated cell death was
proliferation even in low doses of curcumin
accompanied by characteristic morphologi-
is due to the inhibitory effect of the curcu-
cal changes like nuclear condensation and
min by inhibition of various cytokines leads
formation of apoptotic bodies, when exam-
to apoptosis and involved in tumor prolif-
ined under phase contrast microscope.
eration or inhibiting RNA transcription
The present findings illustrate that cur-
rather than direct inhibition of the telom-
cumin induces the release of cytochrome c
erase activity. Therefore, telomerase inhibi-
to translocate from mitochondria to cytosol
tion by curcumin can be interpreted as an
at 3.5 µM concentration. Moreover, cyto-
important event that leads to apoptosis.
26

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EXCLI Journal 2009;8:20-29 – ISSN 1611-2156
Received: August 09, 2008, accepted: January 18, 2009, published: January 21, 2009

Thus, inhibition of hTERT could be a pos-
Chakraborty S, Ghosh U, Bhattacharya NP,
sible potential therapeutic agent to induce
Bhattacharya RK, Roy M. Inhibition of te-
cell death in tumor cells.
lomerase activity and induction of apoptosis

by curcumin in K562 cells. Mutat Res
CONCLUSION
2006;596: 81-90.


In conclusion, our work reveals that
Chan WH, Wu HY, Chang WH. Dosage
curcumin could significantly inhibit telom-
effects of curcumin on cell death types in a
erase activity and induce apoptosis in
human osteoblast cell line. Food Chem
P388D1 cells. Although, the modulation of
Toxicology 2006;44:1362- 71.
telomerase expression by curcumin in can-

cer cells is poorly understood. Therefore,
Cho JW, Lee KS, Kim CW. Curcumin at-
curcumin may inhibit cancer cell growth
tenuates the expression of IL-1beta, IL-6,
and induce apoptosis via reducing telom-
and TNF-alpha as well as cyclin E in TNF-
erase expression.The present investigation
alpha-treated HaCaT cells; NF-kappaB and
suggests that even low dose of curcumin is
MAPKs as potential upstream targets. Int J
sufficient to develop curcumin as possible
Mol Med 2007;19:469-74.
potential universal antineoplastic agent.


Cui SX, Qu XJ, Xie YY, Zhou L, Nakata
ACKNOWLEDGEMENT
M, Makuuchi M, Tang W. Curcumin inhib-

its telomerase activity in human cancer cell
Financial assistance provided by Indian
lines. Int J Mol Med 2006;18:227–31.
Council of Medical Research, New-Delhi.

India. (Research Grant: IRIS (ID No: 2005-
D'Incalci M, Steward WP, Gescher AJ. Use
02310); 3/2/2/79/2005/NCD-III).
of cancer chemopreventive phytochemicals

as antineoplastic agents. Lancet Oncol
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EXCLI Journal 2009;8:20-29 – ISSN 1611-2156
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