Celastrol targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent cytotoxicity in tumor cells

BMC Cancer

Volumn 11, Issue , 2011, Pages

  Chen, Guozhu ^a   Zhang, Xuhui ^a   Zhao, Ming ^a   Wang, Yan ^a   Cheng, Xiang ^a   Wang, Di ^a   Xu, Yuanji ^a   Du, Zhiyan ^a   Yu, Xiaodan ^a  

^a INSTITUTE OF BASIC MEDICAL SCIENCES   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCYSTEINE; ANTHRA[1,9 CD]PYRAZOL 6(2H) ONE; CASPASE 3; CASPASE 9; CATALASE; CELASTROL; CELL CYCLE PROTEIN 37; CYCLIN DEPENDENT KINASE 4; CYTOCHROME C; EPIDERMAL GROWTH FACTOR RECEPTOR; HEAT SHOCK PROTEIN 90; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PROTEIN BAD; PROTEIN KINASE B; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); STRESS ACTIVATED PROTEIN KINASE; THIOREDOXIN; ANTINEOPLASTIC AGENT; MITOGEN ACTIVATED PROTEIN KINASE KINASE 4; TRIPTERINE; TRITERPENE;

ABSORPTION SPECTROSCOPY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CELL CYCLE ARREST; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL STRAIN HEPG2; CELLULAR DISTRIBUTION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG CYTOTOXICITY; FLOW CYTOMETRY; GROWTH INHIBITION; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRION; NECROSIS; PROTEIN CLEAVAGE; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; TUMOR CELL; WESTERN BLOTTING; CELL SURVIVAL; DOSE RESPONSE; DRUG ANTAGONISM; DRUG EFFECT; HUMAN; METABOLISM; NEOPLASM; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL LINE, TUMOR; CELL SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTRON TRANSPORT COMPLEX I; HEP G2 CELLS; HSP90 HEAT-SHOCK PROTEINS; HUMANS; MAP KINASE KINASE 4; NEOPLASMS; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION; TRITERPENES;

EID: 79955855304     PISSN: None     EISSN: 14712407     Source Type: Journal    
DOI: 10.1186/1471-2407-11-170     Document Type: Article

References (50)

1. Allison AC, Cacabelos R, Lombardi VR, Alvarez XA, Vigo C. Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 2001, 25:1341-1357. 10.1016/S0278-5846(01)00192-0, 11513350.
2. Jung HW, Chung YS, Kim YS, Park YK. Celastrol inhibits production of nitric oxide and proinflammatory cytokines through MAPK signal transduction and NF-kappaB in LPS-stimulated BV-2 microglial cells. Exp Mol Med 2007, 39:715-721.
3. Chow AM, Brown IR. Induction of heat shock proteins in differentiated human and rodent neurons by celastrol. Cell Stress Chaperones 2007, 12:237-244. 10.1379/CSC-269.1, 1971233, 17915556.
4. Kim DH, Shin EK, Kim YH, Lee BW, Jun JG, Park JH, Kim JK. Suppression of inflammatory responses by celastrol, a quinone methide triterpenoid isolated from Celastrus regelii. Eur J Clin Invest 2009, 39:819-827. 10.1111/j.1365-2362.2009.02186.x, 19549173.
5. Nagase M, Oto J, Sugiyama S, Yube K, Takaishi Y, Sakato N. Apoptosis induction in HL-60 cells and inhibition of topoisomerase II by triterpene celastrol. Biosci Biotechnol Biochem 2003, 67:1883-1887. 10.1271/bbb.67.1883, 14519971.
6. Abbas S, Bhoumik A, Dahl R, Vasile S, Krajewski S, Cosford ND, Ronai ZA. Preclinical studies of celastrol and acetyl isogambogic acid in melanoma. Clin Cancer Res 2007, 13:6769-6778. 10.1158/1078-0432.CCR-07-1536, 2874065, 18006779.
7. Zhang T, Hamza A, Cao X, Wang B, Yu S, Zhan CG, Sun D. A novel Hsp90 inhibitor to disrupt Hsp90/Cdc37 complex against pancreatic cancer cells. Mol Cancer Ther 2008, 7:162-170. 10.1158/1535-7163.MCT-07-0484, 18202019.
8. Ge P, Ji X, Ding Y, Wang X, Fu S, Meng F, Jin X, Ling F, Luo Y. Celastrol causes apoptosis and cell cycle arrest in rat glioma cells. Neurol Res 2010, 32:94-100. 10.1179/016164109X12518779082273, 19909582.
9. Lu Z, Jin Y, Qiu L, Lai Y, Pan J. Celastrol, a novel HSP90 inhibitor, depletes Bcr-Abl and induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation. Cancer Lett 2010, 290:182-191. 10.1016/j.canlet.2009.09.006, 19819619.
10. He D, Xu Q, Yan M, Zhang P, Zhou X, Zhang Z, Duan W, Zhong L, Ye D, Chen W. The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma. BMC Cancer 2009, 9:343. 10.1186/1471-2407-9-343, 2760578, 19778460.
11. Zhu H, Ding WJ, Wu R, Weng QJ, Lou JS, Jin RJ, Lu W, Yang B, He QJ. Synergistic anti-cancer activity by the combination of TRAIL/APO-2L and celastrol. Cancer Invest 2010, 28:23-32. 10.3109/07357900903095664, 19916747.
12. Chen M, Rose AE, Doudican N, Osman I, Orlow SJ. Celastrol synergistically enhances temozolomide cytotoxicity in melanoma cells. Mol Cancer Res 2009, 7:1946-1953. 10.1158/1541-7786.MCR-09-0243, 19934274.
13. Yang H, Chen D, Cui QC, Yuan X, Dou QP. Celastrol, a triterpene extracted from the Chinese "Thunder of God Vine," is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res 2006, 66:4758-4765. 10.1158/0008-5472.CAN-05-4529, 16651429.
14. Huang Y, Zhou Y, Fan Y, Zhou D. Celastrol inhibits the growth of human glioma xenografts in nude mice through suppressing VEGFR expression. Cancer Lett 2008, 264:101-106. 10.1016/j.canlet.2008.01.043, 18343027.
15. Zhang T, Li Y, Yu Y, Zou P, Jiang Y, Sun D. Characterization of celastrol to inhibit hsp90 and cdc37 interaction. J Biol Chem 2009, 284:35381-35389. 10.1074/jbc.M109.051532, 2790967, 19858214.
16. Hieronymus H, Lamb J, Ross KN, Peng XP, Clement C, Rodina A, Nieto M, Du J, Stegmaier K, Raj SM, Maloney KN, Clardy J, Hahn WC, Chiosis G, Golub TR. Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell 2006, 10:321-330. 10.1016/j.ccr.2006.09.005, 17010675.
17. Chadli A, Felts SJ, Wang Q, Sullivan WP, Botuyan MV, Fauq A, Ramirez-Alvarado M, Mer G. Celastrol inhibits Hsp90 chaperoning of steroid receptors by inducing fibrillization of the Co-chaperone p23. J Biol Chem 2010, 285:4224-4231. 10.1074/jbc.M109.081018, 2823561, 19996313.
18. Sethi G, Ahn KS, Pandey MK, Aggarwal BB. Celastrol, a novel triterpene, potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-kappaB-regulated gene products and TAK1-mediated NF-kappaB activation. Blood 2007, 109:2727-2735.
19. Lee JH, Koo TH, Yoon H, Jung HS, Jin HZ, Lee K, Hong YS, Lee JJ. Inhibition of NF-kappa B activation through targeting I kappa B kinase by celastrol, a quinone methide triterpenoid. Biochem Pharmacol 2006, 72:1311-1321. 10.1016/j.bcp.2006.08.014, 16984800.
20. Pham AN, Blower PE, Alvarado O, Ravula R, Gout PW, Huang Y. Pharmacogenomic approach reveals a role for the x(c)- cystine/glutamate antiporter in growth and celastrol resistance of glioma cell lines. J Pharmacol Exp Ther 2010, 332:949-958. 10.1124/jpet.109.162248, 20007406.
21. Poyton RO, Ball KA, Castello PR. Mitochondrial generation of free radicals and hypoxic signaling. Trends Endocrinol Metab 2009, 20:332-340. 10.1016/j.tem.2009.04.001, 19733481.
22. Li N, Ragheb K, Lawler G, Sturgis J, Rajwa B, Melendez JA, Robinson JP. Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J Biol Chem 2003, 278:8516-8525. 10.1074/jbc.M210432200, 12496265.
23. Xu W, Ngo L, Perez G, Dokmanovic M, Marks PA. Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell response to histone deacetylase inhibitor. Proc Natl Acad Sci USA 2006, 103:15540-15545. 10.1073/pnas.0607518103, 1592530, 17030815.
24. Inoue M, Sato EF, Nishikawa M, Park AM, Kira Y, Imada I, Utsumi K. Mitochondrial generation of reactive oxygen species and its role in aerobic life. Curr Med Chem 2003, 10:2495-2505. 10.2174/0929867033456477, 14529465.
25. Dias N, Bailly C. Drugs targeting mitochondrial functions to control tumor cell growth. Biochemical Pharmacology 2005, 70:1-12. 10.1016/j.bcp.2005.03.021, 15907809.
26. Islam KN, Kayanoki Y, Kaneto H, Suzuki K, Asahi M, Fujii J, Taniguchi N. TGF-beta1 triggers oxidative modifications and enhances apoptosis in HIT cells through accumulation of reactive oxygen species by suppression of catalase and glutathione peroxidase. Free Radic Biol Med 1997, 22:1007-1017. 10.1016/S0891-5849(96)00493-5, 9034240.
27. Lin SS, Huang HP, Yang JS, Wu JY, Hsia TC, Lin CC, Lin CW, Kuo CL, Gibson Wood W, Chung JG. DNA damage and endoplasmic reticulum stress mediated curcumin-induced cell cycle arrest and apoptosis in human lung carcinoma A-549 cells through the activation caspases cascade- and mitochondrial-dependent pathway. Cancer Lett 2008, 272:77-90. 10.1016/j.canlet.2008.06.031, 18701210.
28. Pan JS, Hong MZ, Ren JL. Reactive oxygen species: a double-edged sword in oncogenesis. World J Gastroenterol 2009, 15:1702-1707. 10.3748/wjg.15.1702, 2668775, 19360913.
29. Dalton TP, Shertzer HG, Puge A. Regulation of gene expression by reactive oxygen. Pharmacol Toxicol 1999, 39:67-101.
30. Fruehauf JP, Meyskens FL. Reactive oxygen species: a breath of life or death?. Clin Cancer Res 2007, 13:789-794. 10.1158/1078-0432.CCR-06-2082, 17289868.
31. Sauer H, Wartenberg M. Reactive oxygen species as signaling molecules in cardiovascular differentiation of embryonic stem cells and tumor-induced angiogenesis. Antioxid Redox Signal 2005, 7:1423-1434. 10.1089/ars.2005.7.1423, 16356105.
32. Simon HU, Haj-Yehia A, Levi-Schaffer F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 2000, 5:415-418. 10.1023/A:1009616228304, 11256882.
33. Fleury C, Mignotte B, Vayssiere JL. Mitochondrial reactive oxygen species in cell death signaling. Biochimie 2002, 84:131-141. 10.1016/S0300-9084(02)01369-X, 12022944.
34. Yu X, Guo ZS, Marcu MG, Neckers L, Nguyen DM, Chen GA, Schrump DS. Modulation of p53, ErbB1, ErbB2, and Raf-1 expression in lung cancer cells by depsipeptide FR901228. J Natl Cancer Inst 2002, 94:504-513.
35. Nakano H, Nakajima A, Sakon-Komazawa S, Piao JH, Xue X, Okumura K. Reactive oxygen species mediate crosstalk between NF-kappaB and JNK. Cell Death Differ 2006, 13:730-737. 10.1038/sj.cdd.4401830, 16341124.
36. Shen HM, Liu ZG. JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species. Free Radic Biol Med 2006, 40:928-939. 10.1016/j.freeradbiomed.2005.10.056, 16540388.
37. Fan J, Xu G, Nagel DJ, Hua Z, Zhang N, Yin G. A model of ischemia and reperfusion increases JNK activity, inhibits the association of BAD and 14-3-3, and induces apoptosis of rabbit spinal neurocytes. Neurosci Lett 2010, 473:196-201. 10.1016/j.neulet.2010.02.045, 20188143.
38. Xiao D, Powolny AA, Singh SV. Benzyl isothiocyanate targets mitochondrial respiratory chain to trigger reactive oxygen species-dependent apoptosis in human breast cancer cells. J Biol Chem 2008, 283:30151-30163. 10.1074/jbc.M802529200, 2573064, 18768478.
39. Bogoyevitch MA, Kobe B. Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases. Microbiology and Molecular Biology Reviews 2006, 70:1061-1095. 10.1128/MMBR.00025-06, 1698509, 17158707.
40. Davis W, Ronai Z, Tew KD. Cellular thiols and reactive oxygen species in drug-induced apoptosis. J Pharmacol Exp Ther 2001, 296:1-6.
41. Afonso V, Santos G, Collin P, Khatib AM, Mitrovic DR, Lomri N, Leitman DC, Lomri A. Tumor necrosis factor-alpha down-regulates human Cu/Zn superoxide dismutase 1 promoter via JNK/AP-1 signaling pathway. Free Radic Biol Med 2006, 41:709-721. 10.1016/j.freeradbiomed.2006.05.014, 16895791.
42. Wang W, Adachi M, Kawamura R, Sakamoto H, Hayashi T, Ishida T, Imai K, Shinomura Y. Parthenolide-induced apoptosis in multiple myeloma cells involves reactive oxygen species generation and cell sensitivity depends on catalase activity. Apoptosis 2006, 11:2225-2235. 10.1007/s10495-006-0287-2, 17051330.
43. Sassa H, Takaishi Y, Terada H. The triterpene celastrol as a very potent inhibitor of lipid peroxidation in mitochondria. Biochem Biophys Res Commun 1990, 172:890-897. 10.1016/0006-291X(90)90759-G, 2241977.
44. Sassa H, Kogure K, Takaishi Y, Terada H. Structural basis of potent antiperoxidation activity of the triterpene celastrol in mitochondria: effect of negative membrane surface charge on lipid peroxidation. Free Radic Biol Med 1994, 17:201-207. 10.1016/0891-5849(94)90075-2, 7982625.
45. Moser C, Lang SA, Stoeltzing O. Heat-shock protein 90 (Hsp90) as a molecular target for therapy of gastrointestinal cancer. Anticancer Res 2009, 29:2031-2042.
46. Chiosis G, Neckers L. Tumor selectivity of Hsp90 inhibitors: the explanation remains elusive. ACS Chem Biol 2006, 1:279-284. 10.1021/cb600224w, 17163756.
47. Miyata Y. Hsp90 inhibitor geldanamycin and its derivatives as novel cancer chemotherapeutic agents. Curr Pharm Des 2005, 11:1131-1138. 10.2174/1381612053507585, 15853661.
48. Clark CB, Rane MJ, El Mehdi D, Miller CJ, Sachleben LR, Gozal E. Role of oxidative stress in geldanamycin-induced cytotoxicity and disruption of Hsp90 signaling complex. Free Radic Biol Med 2009, 47:1440-1449. 10.1016/j.freeradbiomed.2009.08.012, 2767391, 19703551.
49. Samuni Y, Ishii H, Hyodo F, Samuni U, Krishna MC, Goldstein S, Mitchell JB. Reactive oxygen species mediate hepatotoxicity induced by the Hsp90 inhibitor geldanamycin and its analogs. Free Radic Biol Med 2010, 48:1559-1563. 10.1016/j.freeradbiomed.2010.03.001, 20211249.
50. Bandyopadhyay U, Das D, Banerjee RK. Reactive oxygen species: oxidative damage and pathogenesis. Curr Sci India 1999, 77:658-666.