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

Volumn 24, Issue 7, 2003, Pages 1199-1208

  Woo, Ju Hyung ^a   Kim, Young Ho ^a   Choi, Yun Jung ^a   Kim, Dae Gon ^b   Lee, Kyung Seop ^b   Bae, Jae Hoon ^a   Min, Do Sik ^c   Chang, Jong Soo ^d   Jeong, Yong Jin ^a   Lee, Young Han ^e   Park, Jong Wook ^a   Kwon, Taeg Kyu ^a  

^a Keimyung University   (South Korea)

^b Dongguk University College of Medicine   (South Korea)

^c The Catholic University of Korea   (South Korea)

^d Daejin University   (South Korea)

^e Yeungnam University College of Medicine   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCYSTEINE; BENZYLOXYCARBONYLVALYLALANYLASPARTYL FLUOROMETHYL KETONE; CASPASE 3; CASPASE INHIBITOR; CURCUMA LONGA EXTRACT; CURCUMIN; CYCLOSPORIN A; CYTOCHROME C; DNA FRAGMENT; INHIBITOR OF APOPTOSIS PROTEIN; PHOSPHOLIPASE C; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN KINASE B; REACTIVE OXYGEN METABOLITE;

ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CELL DAMAGE; CELL DEATH; CELL SURVIVAL; CONTROLLED STUDY; CYTOTOXICITY; DOSE RESPONSE; DOWN REGULATION; DRUG EFFECT; ENZYME ACTIVATION; ENZYME DEGRADATION; ENZYME INACTIVATION; ENZYME INHIBITION; ENZYME RELEASE; HUMAN; HUMAN CELL; INHIBITION KINETICS; KIDNEY CARCINOMA; MOLECULAR MECHANICS; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; RHIZOME;

ANTINEOPLASTIC AGENTS; APOPTOSIS; BCL-2-ASSOCIATED X PROTEIN; BCL-X PROTEIN; BLOTTING, WESTERN; CARCINOMA, RENAL CELL; CASPASES; CURCUMIN; CYTOCHROME C GROUP; DOWN-REGULATION; ENZYME ACTIVATION; ENZYME INHIBITORS; FREE RADICAL SCAVENGERS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INHIBITOR OF APOPTOSIS PROTEINS; KIDNEY NEOPLASMS; MITOCHONDRIA; POLY(ADP-RIBOSE) POLYMERASES; PROTEIN-SERINE-THREONINE KINASES; PROTEINS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; PROTO-ONCOGENE PROTEINS C-BCL-2; REACTIVE OXYGEN SPECIES; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; TUMOR CELLS, CULTURED;

EID: 0042169007     PISSN: 01433334     EISSN: None     Source Type: Journal    
DOI: 10.1093/carcin/bgg082     Document Type: Article

References (46)

1. Ammon,H.P. and Wahl,M.A. (1991) Phamacology of Curcuma longa. Planta Med., 57, 1-7.
2. Huang,M.T., Smart,R.C., Wong,C.Q. and Conney,A.H. (1988) Inhibitory effect of curcumin, chlorogenic acid, caffeic acid and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res., 48, 5941-5946.
3. Huang,M.T., Newmark,H.L. and Frenkel,K. (1997) Inhibitory effects of curcumin on tumorigenesis in mice. J. Cell Biochem. Suppl., 27, 26-34.
4. Mehta,K., Pantazis,P., McQueen,T. and Aggarwal,B.B. (1997) Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell lines. Anticancer Drugs, 8, 470-481.
5. Huang,M.T., Lou,Y.R., Ma,W., Newmark,H.L., Reuhl,K.R. and Conney,A.H. (1994) Inhibitory effects of dietary curcumin on forestomach, duodenal and colon carcinogenesis in mice. Cancer Res., 54, 5841-5847.
6. Kelloff,G.J., Boone,C.W., Crowell,J.A., Steele,V.E., Lubet,R. and Sigman,C.C. (1994) Chemopreventive drug development: perspectives and progress. Cancer Epidemiol. Biomarkers Prev., 3, 85-98.
7. Liu,J.Y., Lin,S.J. and Lin,J.K. (1993) Inhibitory effects of curcumin on protein kinase C activity induced by 12-O-tetradecanoyl-phorbol-13-acetate in NIH 3T3 cells. Carcinogenesis, 14, 857-861.
8. Huang,T.S., Lee,S.C. and Lin,J.K. (1991) Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells. Proc. Natl Acad. Sci. USA, 88, 5292-5296.
9. Huang,M.T., Lysz,T., Ferraro,T., Abidi,T.F., Laskin,J.D. and Conney,A.H. (1991) Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Res., 51, 813-819.
10. Kim,M.S., Kang,H.J. and Moon,A. (2001) Inhibition of invasion and induction of apoptosis by curcumin in H-ras-transformed MCF10A human breast epithelial cells. Arch. Pharm. Res., 24, 349-354
11. Bhaumik,S., Anjum,R., Rangaraj,N., Pardhasaradhi,B.V. and Khar,A. (1999) Curcumin mediated apoptosis in AK-5 tumor cells involves the production of reactive oxygen intermediates. FEBS Lett., 456, 311-314.
12. Kehrer,J.P. (1993) Free radicals as mediators of tissue injury and disease. Crit. Rev. Toxicol., 23, 21-48.
13. Shiraishi,F., Curtis,L.M., Truong,L., Poss,K., Visner,G.A., Madsen,K., Nick,H.S. and Agarwal,A. (2000) Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis. Am. J. Physiol. Renal Physiol., 278, F726-F736.
14. Amato,R.J. (2000) Chemotherapy for renal cell carcinoma. Semin. Oncol., 27, 177-186
15. Jiang,M.C., Yang-Yen,H.F., Yen,J.J. and Lin,J.K. (1996) Curcumin induces apoptosis in immortalized NIH 3T3 and malignant cancer cell lines. Nutr. Cancer, 26, 111-120.
16. LeBel,C.P., Ischiropoulos,H. and Bondy,S.C. (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem. Res. Toxicol., 5, 227-231.
17. Ischiropoulos,H., Gow,A., Thom,S.R., Kooy,N.W., Royall,J.A. and Crow,J.P. (1999) Detection of reactive nitrogen species using 2,7-dichlorodihydrofluorescein and dihydrorhodamine 123. Methods Enzymol., 301, 367-373.
18. Chomczynski,P. and Sacchi,N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem., 162, 156-159.
19. Desagher,S., Osen-Sand,A., Nichols,A., Eskes,R., Montessuit,S., Lauper,S., Maundrell,K., Antonsson,B. and Martinou,J.C. (1999) Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis. J. Cell Biol., 144, 891-901.
20. Bae,S.S., Perry,D.K., Oh,Y.S., Choi,J.H., Galadari,S.H., Ghayur,T., Ryu,S.H., Hannun,Y.A. and Suh,P.G. (2000) Proteolytic cleavage of phospholipase C-gammal during apoptosis in Molt-4 cells. FASEB J., 14, 1083-1092.
21. Yu,R., Mandlekar,S. and Kong,A.T. (2000) Molecular mechanisms of butylated hydroxylanisole-induced toxicity: induction of apoptosis through direct release of cytochrome c. Mol. Pharmacol., 58, 431-437.
22. Thompson,C.B. (1995) Apoptosis in the pathogenesis and treatment of disease. Science, 267, 1456-1462.
23. Jacobson,M.D. (1996) Reactive oxygen species and programmed cell death. Trends Biochem. Sci., 21, 83-86.
24. Deneke,S.M. (2000) Thiol-based antioxidants. Curr. Top Cell Reg., 36, 151-180.
25. Kennedy,S.G., Kandel,E.S., Cross,T.K. and Hay,N. (1999) Akt/Protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Mol. Cell. Biol., 19, 5800-5810.
26. Zhou,H., Li,X.M., Meinkoth,J. and Pittman,R.N. (2000) Akt regulates cell survival and apoptosis at a postmitochondrial level. J. Cell Biol., 151, 483-494.
27. Alessi,D.R., James,S.R., Downes,C.P., Holmes,A.B., Gaffney,P.R., Reese,C.B. and Cohen,P. (1997) Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha. Curr. Biol., 7, 261-269.
28. Stephens,L., Anderson,K., Stokoe,D. et al. (1998) Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B. Science, 279, 710-714.
29. Rokudai,S., Fujita,N., Hashimoto,Y. and Tsuruo,T. (2000) Cleavage and inactivation of antiapoptotic Akt/PKB by caspases during apoptosis. J. Cell Physiol., 182, 290-296.
30. Datta,S.R., Dudek,H., Tao,X., Masters,S., Fu,H., Gotoh,Y. and Greenberg,M.E. (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell, 91, 231-241.
31. Li,P., Nijhawan,D., Budihardjo,I., Srinivasula,S.M., Ahmad,M., Alnemri,E.S. and Wang,X. (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell, 91, 479-489.
32. Adams,J.M. and Cory,S. (1998) The Bcl-2 protein family: arbiters of cell survival. Science, 281, 1322-1326.
33. Nomura,M., Shimizu,S., Ito,T., Narita,M., Matsuda,H. and Tsujimoto,Y. (1999) Apoptotic cytosol facilitates Bax translocation to mitochondria that involves cytosolic factor regulated by Bcl-2. Cancer Res., 59, 5542-5548.
34. Murphy,K.M., Ranganathan,V., Farnsworth,M.L., Kavallaris,M. and Lock,R.B. (2000) Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. Cell Death Differ., 7, 102-111.
35. Deveraux,Q.L. and Reed,J.C. (1999) IAP family proteins: suppressors of apoptosis. Genes Dev., 13, 239-252.
36. Roy,N., Deveraux,Q.L., Takahashi,R., Salvesen,G.S. and Reed,J.C. (1997) The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. EMBO J., 16, 6914-6925.
37. Deveraux,Q.L., Leo,E., Stennicke,H.R., Welsh,K., Salvesen,G.S. and Reed,J.C. (1999) Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases. EMBO J., 18, 5242-5251.
38. Simon,H.U., Haj-Yehia,A. and Levi-Schaffer,F. (2000) Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis, 5, 415-418.
39. Cardone,M.H., Roy,N., Stennicke,H.R., Salvesen,G.S., Franke,T.F., Stanbridge,E., Frisch,S. and Reed,J.C. (1998) Regulation of cell death protease caspase-9 by phosphorylation. Science, 282, 1318-1321.
40. Piwocka,K., Bielak-Mijewska,A. and Sikora,E. (2002) Curcumin induces caspase-3-independent apoptosis in human multidrug-resistant cells. Ann. NY Acad. Sci., 973, 250-254.
41. Piwocka,K., Zablocki,K., Wieckowski,M.R., Skierski,J., Feiga,I., Szopa,J., Drela,N., Wojtczak,L. and 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, 299-307.
42. Piwocka,K., Jaruga,E., Skierski,J., Gradzka,I. and Sikora,E. (2001) Effect of glutathione depletion on caspase-3 independent apoptosis pathway induced by curcumin in Jurkat cells. Free Radic. Biol. Med., 31, 670-678.
43. Jaruga,E., Bielak-Zmijewska,A., Sikora,E., Skierski,J., Radziszewska,E., Piwocka,K. and Bartosz,G. (1998) Glutathione-independent mechanism of apoptosis inhibition by curcumin in rat thymocytes. Biochem. Pharmacol., 56, 961-965.
44. Perkins,S., Verschoyle,R.D., Hill,K., Parveen,I., Threadgill,M.D., Sharma,R.A., Williams,M.L., Steward,W.P. and Gescher,A.J. (2002) Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+ mouse, a model of familial adenomatous polyposis. Cancer Epidemiol. Biomarkers Prev., 11, 535-540.
45. Shoba,G., Joy,D., Joseph,T., Majeed,M., Rajendran,R. and Srinivas,P.S. (1998) Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med., 64, 353-356
46. Sharma,R.A., McLelland,H.R., Hill,K.A., Ireson,C.R., Euden,S.A. and Manson,M.M., Pirmohamed,M., Marnett,L.J., Gescher,A.J. and Steward,W.P. (2001) Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin. Cancer Res., 7, 1894-1900.