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Received: 2008-08-03

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Journal of Zhejiang University SCIENCE B 2009 Vol.10 No.2 P.93-102


Curcumin induces apoptosis through the mitochondria-mediated apoptotic pathway in HT-29 cells

Author(s):  Jin-bo WANG, Li-li QI, Shui-di ZHENG, Tian-xing WU

Affiliation(s):  Department of Chemistry, College of Science, Zhejiang University, Hangzhou 310027, China; more

Corresponding email(s):   wutx@nit.zju.edu.cn

Key Words:  Curcumin, Apoptosis, Mitochondrial pathway, HT-29 cells

Jin-bo WANG, Li-li QI, Shui-di ZHENG, Tian-xing WU. Curcumin induces apoptosis through the mitochondria-mediated apoptotic pathway in HT-29 cells[J]. Journal of Zhejiang University Science B, 2009, 10(2): 93-102.

@article{title="Curcumin induces apoptosis through the mitochondria-mediated apoptotic pathway in HT-29 cells",
author="Jin-bo WANG, Li-li QI, Shui-di ZHENG, Tian-xing WU",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Curcumin induces apoptosis through the mitochondria-mediated apoptotic pathway in HT-29 cells
%A Jin-bo WANG
%A Li-li QI
%A Shui-di ZHENG
%A Tian-xing WU
%J Journal of Zhejiang University SCIENCE B
%V 10
%N 2
%P 93-102
%@ 1673-1581
%D 2009
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0820238

T1 - Curcumin induces apoptosis through the mitochondria-mediated apoptotic pathway in HT-29 cells
A1 - Jin-bo WANG
A1 - Li-li QI
A1 - Shui-di ZHENG
A1 - Tian-xing WU
J0 - Journal of Zhejiang University Science B
VL - 10
IS - 2
SP - 93
EP - 102
%@ 1673-1581
Y1 - 2009
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0820238

Objective: To investigate the effects of curcumin on release of cytochrome c and expressions of Bcl-2, Bax, Bad, Bcl-xL, caspase-3, poly ADP-ribose polymerase (PARP), and survivin of HT-29 cells. Methods: HT-29 cells were treated with curcumin (0~80 μmol/L) for 24 h. The release of cytochrome c from the mitochondria and the apoptosis-related proteins Bax, Bcl-2, Bcl-xL, Bad, caspase-3, PARP, and survivin were determined by Western blot analysis and their mRNA expressions by reverse transcriptase-polymerase chain reaction (RT-PCR). Results: curcumin significantly induced the growth inhibition and apoptosis of HT-29 cells. A decrease in expressions of Bcl-2, Bcl-xL and survivin was observed after exposure to 10~80 μmol/L curcumin, while the levels of Bax and Bad increased in the curcumin-treated cells. curcumin also induced the release of cytochrome c, the activation of caspase-3, and the cleavage of PARP in a dose-dependent manner. Conclusion: These data suggest that curcumin induced the HT-29 cell apoptosis possibly via the mitochondria-mediated pathway.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1] Aggarwal, S., Ichikawa, H., Takada, Y., Sandur, S.K., Shishodia, S., Aggarwal, B.B., 2006. Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IκBα kinase and Akt activation. Mol. Pharmacol., 69(1):195-206.

[2] Bae, J.H., Park, J.W., Kwon, T.K., 2003. Ruthenium red, inhibitor of mitochondrial Ca2+ uniporter, inhibits curcumin induced apoptosis via the prevention of intracellular Ca2+ depletion and cytochrome c release. Biochem. Biophys. Res. Commun., 303(4):1073-1079.

[3] Bhaumik, S., Jyothi, M.D., Khar, A., 2000. Differential modulation of nitric oxide production by curcumin in host macrophages and NK cells. FEBS Lett., 483(1): 78-82.

[4] Cao, J., Liu, Y., Jia, L., Zhou, H.M., Kong, Y., Yang, G., Jiang, L.P., Li, Q.J., Zhong, L.F., 2007. Curcumin induces apoptosis through mitochondrial hyperpolarization and mtDNA damage in human hepatoma G2 cells. Free Radic. Biol. Med., 43(6):968-975.

[5] Chadalapaka, G., Jutooru, I., Chintharlapalli, S., Papineni, S., Smith, R., Li, X., Safe, S., 2008. Curcumin decreases specificity protein expression in bladder cancer cells. Cancer Res., 68(13):5345-5354.

[6] Chen, C.Y., Liu, T.Z., Liu, Y.W., Tseng, W.C., Liu, R.H., Lu, F.J., Lin, Y.S., Chen, C.H., 2007. 6-Shogaol (alkanone from Ginger) induces apoptotic cell death of human hepatoma p53 mutant Mahlavu subline via an oxidative stress-mediated caspase-dependent mechanism. J. Agric. Food Chem., 55(3):948-954.

[7] Chen, J.H., Cao, J.L., Chu, Y.L., Wang, Z.L., Yang, Z.T., Wang, H.L., 2008. T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes. J. Zhejiang Univ. Sci. B, 9(6):455-463.

[8] Cory, S., Adams, J.M., 2002. The Bcl-2 family: regulators of the cellular life-or-death switch. Nat. Rev. Cancer, 2(9): 647-656.

[9] Desai, B.N., Myers, B.R., Schreiber, S.L., 2002. FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction. Proc. Natl. Acad. Sci. USA, 99(7):4319-4324.

[10] Gao, X., Kuo, J., Jiang, H., Deeb, D., Liu, Y., Divine, G., Chapman, R.A., Dulchavsky, S.A., Gautam, S.C., 2004. Immunomodulatory activity of curcumin: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro. Biochem. Pharmacol., 68(1):51-61.

[11] Green, D.R., 2000. Apoptotic pathways: paper wraps stone blunts scissors. Cell, 102(1):1-4.

[12] Grishko, V., Rachek, L., Musiyenko, S., Ledoux, S.P., Wilson, G.L., 2005. Involvement of mtDNA damage in free fatty acid-induced apoptosis. Free Radic. Biol. Med., 38(6): 755-762.

[13] Khor, T.O., Gul, Y.A., Ithnin, H., Seow, H.F., 2006. A comparative study of the expression of Wnt-1, WISP-1, survivin and cyclin-D1 in colorectal carcinoma. Int. J. Colorectal Dis., 21(4):291-300.

[14] Kluck, R.M., Bossy-Wetzel, E., Green, D.R., Newmeyer, D.D., 1997. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science, 275(5303):1132-1136.

[15] Lam, A.K., Saleh, S., Smith, R.A., Ho, Y., 2008. Quantitative analysis of survivin in colorectal adenocarcinoma: increased expression and correlation with telomerase activity. Human Pathol., 39(8):1229-1233.

[16] Li, F., Brattain, M.G., 2006. Role of the survivin gene in pathophysiology. Am. J. Pathol., 169(1):1-10.

[17] Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S.M., Ahmad, M., Alnemri, E.S., Wang, X., 1997. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell, 91(4):479-489.

[18] Moiseeva, E.P., Almeida, G.M., Jones, G.D.D., Manson, M.M., 2007. Extended treatment with physiologic concentrations of dietary phytochemicals results in altered gene expression, reduced growth, and apoptosis of cancer cells. Mol. Cancer Ther., 6(11):3071-3079.

[19] Newman, D.J., Cragg, G.M., Snader, K.M., 2003. Natural products as sources of new drugs over the period 1981-2002. J. Nat. Prod., 66(7):1022-1037.

[20] Pan, M.H., Chang, W.L., Lin-Shiau, S.Y., Ho, C.T., Lin, J.K., 2001. Induction of apoptosis by garcinol and curcumin through cytochrome c release and activation of caspases in human leukemia HL-60 cells. J. Agric. Food Chem., 49(3):1464-1474.

[21] Piwocka, K., Zabłocki, K., Wieckowski, M.R., Skierski, J., Feiga, I., Szopa, J., Drela, N., Wojtczak, L., Sikora, E., 1999. A novel apoptosis-like pathway, independent of mitochondria and caspases, induced by curcumin in human lymphoblastoid T (Jurkat) cells. Exp. Cell Res., 249(2):299-307.

[22] Porn-Ares, M.I., Chow, S.C., Slotte, J.P., Orrenius, S., 1997. Induction of apoptosis and potentiation of TNF and Fas-mediated apoptosis in U937 cells by the xanthogenate compound D609. Exp. Cell Res., 235(1):48-54.

[23] Rashmi, R., Santhosh Kumar, T.R., Karunagaran, D., 2003. Human colon cancer cells differ in their sensitivity to curcumin-induced apoptosis and heat shock protects them by inhibiting the release of apoptosis-inducing factor and caspases. FEBS Lett., 538(1-3):19-24.

[24] Reed, J.C., 1998. Bcl-2 family proteins. Oncogene, 17(25): 3225-3236.

[25] Salvioli, S., Ardizzoni, A., Franceschi, C., Cossarizza, A., 1997. JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess ΔΨ changes in intact cells: implications for studies on mitochondrial functionality during apoptosis. FEBS Lett., 411(1):77-82.

[26] Scott, D.W., Loo, G., 2004. Curcumin-induced GADD153 gene up-regulation in human colon cancer cells. Carcinogenesis, 25(11):2155-2164.

[27] Sen, S., Sharma, H., Singh, N., 2005. Curcumin enhances Vinorelbine-mediated apoptosis in NSCLC cells by the mitochondrial pathway. Biochem. Biophys. Res. Commun., 331(4):1245-1252.

[28] Shang, T., Joseph, J., Hillard, C.J., Kalyanaraman, B., 2005. Death-associated protein kinase as a sensor of mitochondrial membrane potential: role of lysosome in mitochondrial toxin-induced cell death. J. Biol. Chem., 280(41):34644-34653.

[29] Sharma, R.A., Gescher, A.J., Steward, W.P., 2005. Curcumin: the story so far. Eur. J. Cancer, 41(13):1955-1968.

[30] Shi, M., Cai, Q., Yao, L., Mao, Y., Ming, Y., Ouyang, G., 2006. Antiproliferation and apoptosis induced by curcumin in human ovarian cancer cells. Cell Biol. Internat., 30(3):221-226.

[31] Shishodia, S., Amin, H.M., Lai, R., Aggarwal, B.B., 2005a. Curcumin (diferuloylmethane) inhibits constitutive NF-κB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Biochem. Pharmacol., 70(5):700-713.

[32] Shishodia, S., Sethi, G., Aggarwal, B.B., 2005b. Curcumin: getting back to the roots. Ann. N. Y. Acad. Sci., 1056(1):206-217.

[33] Song, G., Mao, Y.B., Cai, Q.F., Yao, L.M., Ouyang, G.L., Bao, D., 2005. Curcumin induces human HT-29 colon adenocarcinoma cell apoptosis by activating p53 and regulating apoptosis-related protein expression. Braz. J. Med. Biol. Res., 38(12):1791-1798.

[34] Suzuki, A., Ito, T., Hayashida, M., Hayasaki, Y., Tuutomi, Y., Akahane, K., Nakano, T., Miura, M., Shiraki, K., 2000. Survivin initiates procaspase-3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death. Oncogene, 19(10):1346-1353.

[35] Tan, H.Y., Liu, J., Wu, S.M., Luo, H.S., 2005. Expression of a novel apoptosis inhibitor—survivin in colorectal carcinoma. World J. Gastroenterol., 11(30):4689-4692.

[36] Wang, X., 2001. The expanding role of mitochondria in apoptosis. Genes Dev., 15(22):2922-2933.

[37] Watson, A.J.M., 2006. An overview of apoptosis and the prevention of colorectal cancer. Crit. Rev. Oncol. Hematol., 57(2):107-121.

[38] Woo, J.H., Kim, Y.H., Choi, Y.J., Kim, D.G., Lee, K.S., Bae, J.H., Mindo, S., Chang, J.S., Jeong, Y.J., Lee, Y.H., et al., 2003. Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-xL and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis, 24(7):1199-1208.

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