Curcumin suppresses the dynamic instability of
microtubules, activates the mitotic checkpoint and
induces apoptosis in MCF-7 cells
Mithu Banerjee, Parminder Singh and Dulal Panda
Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
Introduction
Curcumin, a natural product found in the rhizome of
Curcuma longa, is emerging as an important anticancer
agent on account of its manifold clinical applications
[1–5]. Although the phase I clinical trial of curcumin
for the prevention of colon cancer has already been
completed (clinicaltrials.gov Identifier: NCT00027495),
clinical trials to determine its efficacy in the treat-
ment of rectal cancer (clinicaltrials.gov Identifier:
NCT00745134), advanced pancreatic cancer (clinicaltri-
als.gov Identifier: NCT00094445), colorectal can-
cer (clinicaltrials.gov Identifier: NCT00973869) and
multiple myeloma (clinicaltrials.gov Identifier: NCT-
00113841) are currently in progress. In addition, the
potential of curcumin to reduce the symptomatic side
effects of chemoradiation in patients suffering from
non-small cell lung cancer (clinicaltrials.gov Identifier:
NCT01048983) is under clinical investigation. Curcu-
min has also entered into a phase II clinical trial for
Keywords
apoptosis; BubR1; combination study;
delayed mitosis; dynamic instability
Correspondence
D. Panda, Department of Biosciences &
Bioengineering, Indian Institute of
Technology Bombay, Powai,

Abbreviations
CI, combination index; FITC, fluorescein isothiocyanate; PI, propidium iodide.
FEBS Journal 277 (2010) 3437–3448 ª 2010 The Authors Journal compilation ª 2010 FEBS 3437
advanced pancreatic cancer [2] and a phase III clinical
trial in combination with gemcitabine and celebrex for
the treatment of metastatic colon cancer [2]. Curcumin
inhibits tumor growth in animal models [3]. Further,
the uptake of high doses of curcumin in both animals
and humans has been found to be nonhazardous and
relatively nontoxic [4,5]. Curcumin has also been found
to be an effective stress reliever and neuroprotective
agent [6].
Curcumin has been shown to inhibit the prolifera-
tion of several types of cancer cells in culture, includ-
ing pancreatic, cervical, colon and breast cancer [7–15].
It arrests the cell-cycle progression of human pancre-
atic cancer cells (BxPC-3) and glioma cells (U251) at
the G
2
⁄ M phase of the cell cycle [7,8] and has been
shown to affect the progression of MCF-7 cells
through the G
2
⁄ M phase [9]. Curcumin treatment
caused an increase in the G
0
⁄ G
1
phase of the cell pop-
ulation implying apoptosis in MCF-7 cells [10]. Curcu-

tion inhibitory concentrations, curcumin inhibited
microtubule dynamics in MCF-7 cells without causing
a significant depolymerization of microtubules. How-
ever, high concentrations (‡ 2 · IC
50
) of curcumin
were found to depolymerize both the interphase and
mitotic microtubules in MCF-7 cells. Curcumin treat-
ment perturbed the mitotic spindle network in MCF-7
cells, activated the mitotic checkpoint and delayed
mitotic progression. We present several lines of evi-
dence indicating that curcumin inhibits cell prolifera-
tion by inhibiting microtubule dynamics. The results
suggest that tubulin is one of the major targets for the
antiproliferative activity of curcumin.
Results
Curcumin inhibited the proliferation of MCF-7
cells and induced apoptosis
Consistent with previous studies [9,10,12], curcumin
was found to inhibit the proliferation of MCF-7 cells
in a concentration-dependent manner (Fig. 1A). For
example, 20 and 40 lm curcumin inhibited the prolifer-
ation of MCF-7 cells by 70% and 93%, respectively,
and the half-maximal inhibition of proliferation (IC
50
)
was determined to be 16 ± 0.3 lm. MCF-7 cells were
either treated with the vehicle or different concentra-
tions of curcumin for 48 h. Vehicle-treated MCF-7
cells did not display Annexin V and propidium iodide

B
Fig. 1. Curcumin inhibited the proliferation of MCF-7 cells and induced cell death. (A) MCF-7 cells were treated with different concentrations
of curcumin for one cell cycle and the inhibition of cell proliferation was determined by the sulforhodamine B assay. (B) Curcumin induced
apoptosis in MCF-7 cells. MCF-7 cells were incubated with 0.1% dimethylsulfoxide (control) and different concentrations (12–36 l
M) of curc-
umin for 48 h and then stained with Annexin V ⁄ PI. Scale bar, 10 lm. Curcumin (24 l
M) treatment increased the nuclear accumulation of p53
(C) and p21 (D) in MCF-7 cells. Scale bar, 10 lm.
Tubulin DNA
Merge
Control
Curcumin 24 μ
M
Curcumin 36 μM
Control
Curcumin
0 min
15 min
15 min
25 min
25 min0 min
AB
Fig. 2. Curcumin-perturbed mitotic spindle structures of MCF-7 cells. (A) MCF-7 cells were incubated without or with 24 and 36 lM of curcu-
min for 6 h. Microtubules are shown in red and the nucleus in blue. Scale bar, 10 lm. (B) Curcumin suppressed the reassembly of the cold-
depolymerized mitotic spindle microtubules. The upper and lower panels show growth kinetics of spindle microtubules in the absence or the
presence of 36 l
M curcumin. Scale bar, 10 lm.
M. Banerjee et al. Curcumin suppresses microtubule dynamics
FEBS Journal 277 (2010) 3437–3448 ª 2010 The Authors Journal compilation ª 2010 FEBS 3439
shown). Consistent with a previous study [12], curcu-

reassemble (Fig. 2B). The results showed that cur-
cumin inhibited reassembly of the mitotic spindle
microtubules.
Curcumin suppressed the dynamic instability of
individual microtubules in live MCF-7 cells
Consistent with previous reports [19,20], microtubules
in control MCF-7 cells were found to be highly
dynamic (Fig. 3A). Low concentrations of curcumin (5
and 12 lm) noticeably dampened the dynamic instabil-
ity of the individual microtubules in live MCF-7 cells
(Fig. 3B,C). Curcumin treatment reduced the rate and
extent of both growing and shortening events
(Table 1). For example, 12 lm curcumin reduced the
rates of shortening and growing phases by 39% and
19%, respectively, and reduced the extent of the grow-
ing and shortening phases by 60% and 65%, respec-
tively. Like several other tubulin-targeted agents such
as benomyl, estramustine, epothilone B and paclitaxel
[19–22], curcumin also strongly increased the time that
microtubules spent in the pause state, neither growing
nor shortening detectably, and decreased the time
microtubules spent in the growing or shortening
phases. Curcumin (12 lm) increased the time spent in
the pause state from 28.9% (control) to 71.6%. Fur-
ther, curcumin (12 lm) altered both the time- and
length-based transition frequencies of the interphase
microtubules in MCF-7 cells. The dynamicity (dimer
exchange per unit time from the ends of microtubules)
was reduced by 50% and 72% in the presence of
5 and 12 lm curcumin, respectively.

Further, MCF-7 cells were synchronized in the M
phase of the cell cycle by nocodazole treatment for
20 h. Nocodazole-blocked cells were washed with fresh
medium and subsequently incubated in medium with-
out and with curcumin. Flow cytometry analysis dem-
onstrated that nocodazole-induced mitotic arrest was
gradually released over time for control cells. For
example, the percentage of cells in mitosis was 87%,
53% and 16% in nocodazole-treated control flask
immediately, and 4 and 8 h after release of the noco-
dazole block. However, in the presence of curcumin,
the percentage of cells in the mitotic phase was 83%
and 81% after 4 and 8 h of block release. Thus, treat-
ment of cells with curcumin significantly delayed
release of the mitotic block (Fig. 4A). However, flow
cytometric analysis of the cell cycle using PI staining
showed that there was no significant cell-cycle block
after 24 h of curcumin treatment (Fig. S2).
Microtubule inhibitors are known to induce mitotic
block by activating the spindle assembly checkpoint
proteins [20,23,24]. It has been suggested that a com-
pound may drive the cells towards delayed mitosis
through activation of spindle checkpoint proteins such
as BubR1 [23] and Mad2 [24]. Nocodazole, a well-
known inhibitor of mitosis, led to the accumulation of
Mad2 and BubR1 at the kinetochores (Fig. 4B,C).
Similar to the action of nocodazole, curcumin treat-
ment also activated Mad2 and BubR1 in MCF-7 cells
(Fig. 4B,C).
Curcumin exhibited antagonism with paclitaxel,

a
Shortening rate (lmÆmin
)1
) 23.5 ± 10.4 18.2 ± 5.7
a
14.4 ± 4.95
a
Shortening length (lm) 3.3 ± 1.9 2.1 ± 1.1
a
1.14 ± 0.51
a
Shortening time (min) 0.53 ± 0.18 0.43 ± 0.19 0.28 ± 0.11
a
Pause time (min) 0.72 ± 0.28 1.43 ± 0.35
a
1.82 ± 0.36
a
% Time spent in growing 47.5 ± 9.8 22.7 ± 8.8
a
13.5 ± 7.3
a
% Time spent in shortening 22.4 ± 8.3 18.7 ± 7.9
a
11.6 ± 4.7
a
% Time spent in pause 28.9 ± 11.6 59.5 ± 14.0
a
71.6 ± 13.8
a
Dynamicity (lmÆmin

P < 0.0001;
b
P < 0.001.
M. Banerjee et al. Curcumin suppresses microtubule dynamics
FEBS Journal 277 (2010) 3437–3448 ª 2010 The Authors Journal compilation ª 2010 FEBS 3441
combination with 8 lm curcumin, these concentrations
of vinblastine inhibited proliferation by 44% and 51%,
respectively. The CI values for the combination of
8 lm curcumin with 2 and 3 nm of vinblastine were
estimated to be 0.92 ± 0.23 and 0.97 ± 0.19, respec-
tively. A CI value < 1 indicates a synergistic effect,
1 indicates an additive effect and > 1 indicates an
antagonistic effect [25,26]. The results suggested that
curcumin was antagonistic to paclitaxel, whereas it dis-
played an additive effect with vinblastine in inhibiting
MCF-7 cell proliferation.
Curcumin affected the localization of the kinesin
protein Eg5
Because curcumin produced monopolar spindles in
MCF-7 cells, we examined the effect of curcumin on
the localization of Eg5, a motor protein that plays an
essential role in bipolar spindle formation [27,28]. In
control cells, Eg5 was localized throughout the bipolar
spindle and remained concentrated at the spindle poles
(Fig. 5A). Consistent with a previous study [27], mon-
astrol (50 lm) was found to induce monopolar spindle
formation (Fig. 5B). In monastrol-treated cells, Eg5
mainly localized to the pole of the monoastral spindle
and also diffused all along the monoastral microtu-
bules (Fig. 5B). In the presence of 24 lm curcumin,

0 30 60 90 120 150
0 30 60 90 120 150
0 30 60 90 120 150
0 20 40 60 80 100 120
Fig. 4. Curcumin treatment delayed mitotic progression in MCF-7 cells. (A) MCF-7 cells were incubated with 1.3 lM nocodazole. Nocodazole
was washed off with fresh medium. Cells were incubated in the absence or presence of 35 l
M curcumin for 4 and 8 h and then stained
with PI. DNA content of the cells was quantified by flow cytometry. Nocodazole and curcumin treatment activated Mad2 (B) and BubR1 (C)
in MCF-7 cells. MCF-7 cells were incubated with nocodazole (500 n
M) and curcumin (36 lM) for 24 h and cells were then stained with Mad2
and BubR1 antibodies. Scale bar, 10 lm.
Curcumin suppresses microtubule dynamics M. Banerjee et al.
3442 FEBS Journal 277 (2010) 3437–3448 ª 2010 The Authors Journal compilation ª 2010 FEBS
found to bind to purified tubulin and to perturb
microtubule assembly in vitro [12]. The results together
indicated that curcumin inhibits MCF-7 cell prolifera-
tion by targeting microtubules.
The plus-end-directed motor Eg5 (kinesin spindle
protein) plays an important role in proper chromo-
some separation and the formation of a proper bipolar
spindle [27,28]. Similar to the action of monastrol [27],
curcumin also induced monopolar spindle formation in
association with the perturbation of Eg5 localization
in MCF-7 cells, indicating that curcumin may inhibit
Eg5 function and thereby induce monopolar spindle
formation. Curcumin might inhibit the binding of Eg5
to microtubules and perturb the movement of Eg5
over the microtubules leading to abnormal spindle for-
mation. Alternatively, curcumin might directly interact
with Eg5 and inhibit its function.

of inhibition of cell prolifera-
tion being 20 nm) [30]. In human non-small cell lung
carcinoma cells A549, low concentrations of paclitaxel
(3-6 nm) inhibited cell proliferation without causing
mitotic arrest [31]. Moreover, treatment with a low
concentration of paclitaxel induced abnormal cell for-
mation without the G
2
⁄ M block [32]. A 50% inhibi-
tion of cell growth after 72 h incubation required
3.4 nm paclitaxel and 9.5 nm discodermolide [32].
These concentrations were closer to that required for
aneuploidy induction rather than mitotic arrest [32].
Tubulin
Eg5
DNA Tubulin + Eg5
Tubulin + Eg5 + DNA
A
B
C
Fig. 5. Localization of Eg5 in control and curcumin-treated MCF-7 cells. Cells were treated without and with curcumin for 24 h, fixed, and
co-immunostained with a-tubulin (green), Eg5 antibody (red) and DNA was stained with Hoechst 33258. (A) In control mitotic cells, Eg5
remained mainly concentrated at the poles of the bipolar spindle and to some extent delocalized along the spindle microtubules. (B) In the
presence of 50 l
M monastrol, monopolar spindles were formed. Eg5 localized mainly at the pole of the monopolar spindle and remained dif-
fused along the microtubules in the overlayed image. (C) Curcumin at a concentration of 24 l
M induced monopolar spindle formation. In the
overlain image the Eg5 localized to the centre of the monopolar spindle and also remained dispersed over the microtubules. Scale bar,
10 lm.
M. Banerjee et al. Curcumin suppresses microtubule dynamics

gene p53 is known to induce apoptosis in several types
of cells [40–42]. It has been suggested that p53 is trans-
ported into the nucleus through the microtubule net-
work [40,41]. Compounds that stabilize microtubule
dynamics have been suggested to promote p53 translo-
cation to the nucleus [19,41]. Several antimitotic drugs
have been found to induce apoptosis by inhibiting
microtubule assembly dynamics [43]. Curcumin
suppresses the dynamic instability of microtubules,
therefore, it may enhance nuclear translocation of p53
through the stabilized microtubule track.
Curcumin in combination with vinblastine, a micro-
tubule depolymerizing agent, inhibited cell prolifera-
tion in an additive fashion. However, it antagonized
the action of paclitaxel, a compound that promotes
microtubule assembly; supporting the idea that curcu-
min inhibits cell proliferation by targeting micro-
tubules. The results also indicated that curcumin may be
used in combination with microtubule depolymerizing
agents such as vinblastine to improve the efficacy and
reduce the toxic dose of the drug. It has been found
that an oral intake of curcumin is not toxic to humans
up to 8000 mgÆday
)1
for 3 months [44]. Moreover,
curcumin (C
3
ComplexÔ, Sabinsa Corp., East Wind-
sor, NJ, USA) in single oral doses up to 12 000 mg
was found to be well tolerated in healthy volunteers

medium (dimethylsulfoxide was £ 0.1% v ⁄ v) 24 h after
seeding. Dimethylsulfoxide (0.1%) was used as a vehicle
control.
Cell proliferation assay and mitotic index
calculation
The effect of curcumin on the proliferation of MCF-7 cells
was determined by sulforhodamine B assay [49]. For mito-
tic index calculation, MCF-7 cells were seeded at a density
of 1.0 · 10
5
cellsÆmL
)1
on poly(l-lysine)-coated glass cover-
slips followed by treatment with curcumin for 24 h [20].
The coverslips were centrifuged in a Labofuge 400R cyto-
spin (Heraeus, Hanau, Germany) for 10 min (1200 g at
30 °C) and fixed with 3.7% formaldehyde for 30 min at
37 °C. The cells were permeabilized with methanol and
stained with Hoechst 33258. The number of cells in mitosis
and interphase were counted using the Eclipse TE2000-U
microscope (Nikon, Tokyo, Japan). At least 800 cells were
counted for each set and the experiment was repeated three
times. The numbers of cells at the metaphase and anaphase
stages of the cell cycle were calculated for both the control
and curcumin-treated cells.
Curcumin suppresses microtubule dynamics M. Banerjee et al.
3444 FEBS Journal 277 (2010) 3437–3448 ª 2010 The Authors Journal compilation ª 2010 FEBS
Immunofluorescence microscopy and
transfection
MCF-7 cells (0.6 · 10

processing. MCF-7 cells were transfected with EGFP–
a-tubulin plasmid, as described previously [20] and the
stably transfected MCF-7 cells were maintained in the pres-
ence of the antibiotic G418.
Annexin V
⁄
propidium iodide staining
MCF-7 cells were grown in the absence and presence of dif-
ferent concentrations of curcumin for 48 h and were stained
with Annexin V ⁄ PI, as reported previously [20,48]. The
manufacturer’s protocol was used for staining the cells
using an Annexin V apoptosis detection kit (Santa Cruz
Biotechnology) and processed for microscopy [20,48]. The
cells exhibiting positive Annexin V and PI staining were
seen under microscope using the FITC and PI fluorescence,
differential interference contrast microscopy was used for
visualizing total number of cells.
Cell-cycle analysis
MCF-7 cells were grown in the absence and presence of 25
and 35 lm curcumin for 24 h. The cells were first fixed in
70% ethanol, washed with NaCl ⁄ P
i
and then incubated
with 50 lgÆmL
)1
PI containing 8 lgÆmL
)1
RNase for 2 h at
4 °C. The DNA content of the cells was quantified using a
flow cytometer (FACS Aria; Becton Dickinson, San Jose,

method [50]. The polymeric and the soluble tubulin frac-
tions were run on SDS ⁄ PAGE and electroblotted on
poly(vinylidene difluoride) membranes. The membranes
were probed with mouse monoclonal anti-(a-tubulin IgG)
(1 : 1000) and alkaline phosphatase-conjugated secondary
anti-(mouse IgG) (1 : 5000) (Sigma). The band intensities
were calculated using image j software.
Effects of curcumin on the dynamic instability of
individual microtubules in MCF-7 cells
The effects of curcumin on the dynamic instability of the
interphase microtubules in MCF-7 cells were determined as
described previously [20,51]. Briefly, MCF-7 cells having
stably transfected green fluorescent protein–a-tubulin were
grown on glass coverslips for 24 h. Cells were then incu-
bated in the absence or presence of 5 and 12 lm curcumin
for an additional 24 h. The coverslips were transferred to
glass-bottomed dishes (Prime BioScience, Pandan Loop,
Singapore) containing media without phenol red and were
maintained at 37 °C on a warm stage. Time-lapse imaging
of microtubules was carried out using an FV-500 laser
scanning confocal microscope (Olympus, Tokyo, Japan)
with a 60 · water immersion objective. The images were
acquired at 4 s intervals for a maximum duration of 3 min
using fluoview software (Olympus, Tokyo, Japan). The
M. Banerjee et al. Curcumin suppresses microtubule dynamics
FEBS Journal 277 (2010) 3437–3448 ª 2010 The Authors Journal compilation ª 2010 FEBS 3445
plus end of microtubules was tracked using image j soft-
ware. Life-history traces were obtained by plotting the
length of individual microtubules against time. Length
changes of ‡ 0.5 lm for a minimum of two data points

u
represent the median dose, fraction
affected and fraction unaffected, respectively [27]. Dm was
estimated from the antilog of the X-intercept of the median
effect plot, where X = log (D) versus Y = log (f
a
⁄ f
u
);
which means Dm =10
)(Y-intercept) ⁄ m
, m being the slope of
the median effect plot.
Acknowledgement
The work was partly supported by Swarnajayanti Fel-
lowship (to DP) from the Department of Science and
Technology and partly by a grant from the Council of
Scientific and Industrial Research, Government of
India.
References
1 Shishodia S, Chaturvedi MM & Aggarwal BB (2007)
Role of curcumin in cancer therapy. Curr Probl Cancer
31, 243–305.
2 Hatcher H, Planalp R, Cho J, Torti FM & Torti SV
(2008) Curcumin: from ancient medicine to current clin-
ical trials. Cell Mol Life Sci 65, 1631–1652.
3 Chun KS, Sohn Y, Kim HS, Kim OH, Park KK, Lee
JM, Moon A, Lee SS & Surh YJ (1999) Anti-tumor
promoting potential of naturally occurring diarylhepta-
noids structurally related to curcumin. Mutat Res 428,

RB, Rao CV & Reddy BS (1999) Chemopreventive
effect of curcumin, a naturally occurring anti-inflamma-
tory agent, during the promotion ⁄ progression stages of
colon cancer. Cancer Res 59, 597–601.
12 Gupta KK, Bharne SS, Rathinasamy K, Naik NR &
Panda D (2006) Dietary antioxidant curcumin inhibits
microtubule assembly through tubulin binding. FEBS J
273, 5320–5332.
13 Holy JM (2002) Curcumin disrupts mitotic spindle
structure and induces micronucleation in MCF-7 breast
cancer cells. Mutat Res 518, 71–84.
14 Wolanin K, Magalska A, Mosieniak G, Klinger R,
McKenna S, Vejda S, Sikora E & Piwocka K (2006)
Curcumin affects components of the chromosomal pas-
senger complex and induces mitotic catastrophe in
apoptosis-resistant Bcr-Abl-expressing cells. Mol Cancer
Res 4, 457–469.
15 Dempe JS, Pfeiffer E, Grimm AS & Metzler M (2008)
Metabolism of curcumin and induction of mitotic catas-
trophe in human cancer cells. Mol Nutr Food Res 52,
1074–1081.
Curcumin suppresses microtubule dynamics M. Banerjee et al.
3446 FEBS Journal 277 (2010) 3437–3448 ª 2010 The Authors Journal compilation ª 2010 FEBS
16 Thomas SL, Zhong D, Zhou W, Malik S, Liotta D,
Snyder JP, Hamel E & Giannakakou P (2008) EF24,
a novel curcumin analog, disrupts the microtubule
cytoskeleton and inhibits HIF-1. Cell Cycle 7,
2409–2417.
17 Desai A & Mitchison TJ (1997) Microtubule
polymerization dynamics. Annu Rev Cell Dev Biol 13,

inhibition, G2–M arrest, and apoptosis. Clin Cancer
Res 8, 3512–3519.
26 Chou TC & Talalay P (1984) Quantitative analysis of
dose–effect relationships: the combined effects of multi-
ple drugs or enzyme inhibitors. Adv Enzyme Regul 22,
27–55.
27 Mayer TU, Kapoor TM, Haggarty SJ, King RW,
Schreiber SL & Mitchison TJ (1999) Small molecule
inhibitor of mitotic spindle bipolarity identified in a
phenotype-based screen. Science 286, 971–974.
28 Kwok BH, Yang JG & Kapoor TM (2004) The rate of
bipolar spindle assembly depends on the microtubule-
gliding velocity of the mitotic kinesin Eg5. Curr Biol 14,
1783–1788.
29 Prinz H, Ishii Y, Hirano T, Stoiber T, Camacho Gomez
JA, Schmidt P, Du
¨
ssmann H, Burger AM, Prehn JH,
Gu
¨
nther EG et al. (2003) Novel benzylidene-9(10H)-
HMBAs as highly active antimicrotubule agents.
Synthesis, antiproliferative activity, and inhibition
of tubulin polymerization. J Med Chem 46, 3382–
3394.
30 Wood DL, Panda D, Wiernicki TR, Wilson L, Jordan
MA & Singh JP (1997) Inhibition of mitosis and micro-
tubule function through direct tubulin binding by a
novel antiproliferative naphthopyran LY290181. Mol
Pharmacol 52

Salmon ED (2002) hNuf2 inhibition blocks stable
kinetochore–microtubule attachment and induces mito-
tic cell death in HeLa cells. J Cell Biol 159, 549–555.
40 Chari NS, Pinaire NL, Thorpe L, Medeiros LJ,
Routbort MJ & McDonnell TJ (2009) The p53 tumor
suppressor network in cancer and the therapeutic
modulation of cell death. Apoptosis 14, 336–347.
41 Giannakakou P, Nakano M, Nicolaou KC, O’Brate A,
Yu J, Blagosklonny MV, Greber UF & Fojo T (2002)
Enhanced microtubule-dependent trafficking and p53
nuclear accumulation by suppression of microtubule
dynamics. Proc Natl Acad Sci USA 99, 10855–10860.
42 Kastan MB, Canman CE & Leonard CJ (1995) P53,
cell cycle control and apoptosis: implications for cancer.
Cancer Metastasis Rev 14, 3–15.
43 Este
`
ve MA, Carre
´
M & Braguer D (2007) Microtubules
in apoptosis induction: are they necessary? Curr Cancer
Drug Targets 7, 713–729.
M. Banerjee et al. Curcumin suppresses microtubule dynamics
FEBS Journal 277 (2010) 3437–3448 ª 2010 The Authors Journal compilation ª 2010 FEBS 3447
44 Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF,
Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W
et al. (2001) Phase I clinical trial of curcumin, a
chemopreventive agent, in patients with high-risk
or pre-malignant lesions. Anticancer Res 21, 2895–
2900.

Supporting information
The following supplementary material is available:
Fig. S1. Effect of curcumin on cellular microtubules.
Fig. S2. Effect of curcumin on the progression of
MCF-7 cell cycle.
Fig. S3. Median effect plots for the inhibition of
MCF-7 cell proliferation by (A) curcumin, (B) paclit-
axel and (C) vinblastine.
This supplementary material can be found in the
online version of this article.
Please note: As a service to our authors and readers,
this journal provides supporting information supplied
by the authors. Such materials are peer-reviewed and
may be re-organized for online delivery, but are not
copy-edited or typeset. Technical support issues arising
from supporting information (other than missing files)
should be addressed to the authors.
Curcumin suppresses microtubule dynamics M. Banerjee et al.
3448 FEBS Journal 277 (2010) 3437–3448 ª 2010 The Authors Journal compilation ª 2010 FEBS