Acquired resistance to TRAIL-induced apoptosis in human ovarian cancer cells is conferred by increased turnover of mature caspase-3

Molecular Cancer Therapeutics - Tập 5 Số 3 - Trang 509-521 - 2006
Denis Lane1, Marceline Côté1, Roxanne Grondin1, Marie-Christine Couture1, Alain Piché1
1Département de Microbiologie et Infectiologie, Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Quebec, Canada

Tóm tắt

AbstractLittle is known on how cancer cells can acquire resistance to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). In this study, we established TRAIL-resistant cells from the TRAIL-sensitive human ovarian carcinoma cell line OVCAR3 to evaluate the potential mechanisms of acquired resistance to TRAIL. The selected resistant cells were cross-resistant to Fas ligand but remained sensitive to drug-induced apoptosis. Expression of TRAIL receptors was not altered in TRAIL-resistant OVCAR3 cells. Cleavage of caspase-8 and caspase-3 occurred in both TRAIL-resistant and TRAIL-sensitive cells. However, mature caspase-3 fragments were not detected by immunoblot in TRAIL-resistant cells and caspase-3 activity was significantly inhibited in these cells. The addition of proteasome inhibitors significantly increased TRAIL-induced apoptosis in resistant cells and enhanced the accumulation of mature caspase-3 fragments. Pretreatment with cycloheximide showed that active caspase-3 fragments have a high turnover rate in OVCAR3 R350 cells. X-linked inhibitor of apoptosis down-regulation by RNA interference also increased the accumulation of cleaved caspase-3 intermediates and resensitized TRAIL-resistant cells. Our findings show that altered turnover of mature caspase-3 may lead to acquired TRAIL resistance in ovarian cancer cells. Proteasome and X-linked inhibitor of apoptosis inhibitors could have a role in clinical situations to potentiate the cytotoxic effects of TRAIL in resistant tumor cells. [Mol Cancer Ther 2006;5(3):509–21]

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Tài liệu tham khảo

Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science 1998;281:1305–8.

Hao C, Beguinot F, Condorelli G, et al. Induction and intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apoptosis in human malignant glioma cells. Cancer Res 2001;61:1162–70.

Chang DW, Xing Z, Pan Y, et al. c-Flip-L is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis. EMBO J 2002;21:3704–14.

Ahskenazi A, Pai RC, Fong S, et al. Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 1999;104:155–62.

Walczak H, Miller RE, Ariail K, et al. Tumoricidal activity of tumor necrosis factor-related apoptosis-induced ligand in vivo. Nat Med 1999;5:157–63.

Degli-Esposti MA, Smolak PJ, Walczak H, et al. Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J Exp Med 1997;186:1165–70.

Degli-Esposti MA, Dougall WC, Smolak PJ, et al. The novel receptor TRAIL-R4 induces NF-κ-B and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity 1997;7:813–20.

Marsters SA, Sheridan JP, Pitti RM, et al. A novel receptor for APO2L/TRAIL contains a truncated death domain. Curr Biol 1997;7:1003–6.

Bodmer JL, Holler N, Reynard S, et al. TRAIL receptor-2 signals apoptosis through FADD and caspase-8. Nat Cell Biol 2000;2:241–3.

Kischkel FC, Hellbardt S, Behrmann I, et al. Cytotoxicity-dependent APO-1 (FAS/CD95)-associated proteins from a death-signaling complex (DISC) with the receptor. EMBO J 1995;14:5579–88.

Muzio M, Stockwell BR, Stennicke HR, et al. An induced proximity model for caspase-8 activation. J Biol Chem 1998;273:2926–30.

Deng Y, Lin Y, Wu X. TRAIL-induced apoptosis requires Bax-dependent mitochondrial release of Smac/DIABLO. Genes Dev 2002;16:33–45.

Sun XM, Bratton SB, Butterworth M, et al. Bcl-2 and Bcl-XL inhibit CD95-mediated apoptosis by preventing mitochondrial release of Smac/DIABLO and subsequent inactivation of X-linked inhibitor of apoptosis protein. J Biol Chem 2002;277:11345–51.

LaCasse EC, Baird S, Kormeluk RG, et al. The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene 1998;17:3247–59.

Cummins JM, Kohli M, Rago C, et al. X-linked inhibitor of apoptosis protein (XIAP) is a nonredundant modulator of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in human cancer cells. Cancer Res 2004;64:3006–8.

Takahashi R, Deveraux Q, Tamm I, et al. A single BIR domain of XIAP sufficient for inhibiting caspases. J Biol Chem 1998;273:7787–90.

Deveraux QL, Reed JC. IAP family proteins—suppressors of apoptosis. Genes Dev 1999;13:239–52.

Landis SH, Murray T, Bolden S, et al. Cancer statistics. CA Cancer J Clin 1999;49:8–31.

Partridge EE, Barnes MN. Epithelial ovarian cancer: prevention, diagnosis, and treatment. CA Cancer J Clin 1999;49:297–320.

Lane D, Cartier A, L'Espérance S, et al. Differential induction of apoptosis by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in human ovarian carcinoma cells. Gynecol Oncol 2004;93:594–604.

Vignati S, Codegoni A, Polato F, et al. TRAIL activity in human ovarian cancer cells: potentiation of the action of cytotoxic drugs. Eur J Cancer 2002;38:177–83.

Cuello M, Ettenberg SA, Nau MM, et al. Synergistic induction of apoptosis by the combination of TRAIL and chemotherapy in chemoresistant ovarian cancer cells. Gynecol Oncol 2001;81:380–90.

Siervo-Sassi RR, Marrangoni AM, Feng X, et al. Physiological and molecular effects of Apo2L/TRAIL and cisplatin in ovarian carcinoma cell lines. Cancer Lett 2003;190:61–72.

Piché A, Grim J, Rancourt C, et al. Modulation of Bcl-2 protein expression by an intracellular anti-Bcl-2 single-chain antibody increases drug-induced cytotoxicity in the breast cancer cell line MCF-7. Cancer Res 1998;58:2134–40.

Kim K, Fisher MJ, Xu SQ, et al. Molecular determinants of response to TRAIL in killing of normal and cancer cells. Clin Cancer Res 2000;6:335–46.

Rieger J, Naumann U, Glaser T, et al. APO2 ligand: a novel lethal weapon against malignant glioma? FEBS Lett 1998;427:124–8.

Zhang XD, Franco A, Myers K, et al. Relation of TNF-related protein-inducing ligand (TRAIL) receptor and FLICE-inhibitory protein expression to TRAIL-induced apoptosis of melanoma. Cancer Res 1999;59:2747–53.

Mitsiades N, Poulaki V, Mitsiades C, et al. Ewing's sarcoma family tumors are sensitive to tumor necrosis factor-related apoptosis-inducing ligand and express death receptor 4 and death receptor 5. Cancer Res 2001;61:2704–12.

Jin Z, Mc Donald ER III, Dicker DT, et al. Deficient tumor necrosis factor related apoptosis ligand (TRAIL) death receptor transport to the cell surface in human colon cancer cells selected for resistance to TRAIL-induced apoptosis. J Biol Chem 2004;279:35829–39.

Griffith TS, Chin WA, Jackson GC, et al. Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. J Immunol 1998;161:2833–40.

Deveraux QL, Leo E, Stennicke HR, et al. Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases. EMBO J 1999;18:5242–51.

Suzuki Y, Nakabayashi Y, Takahashi R. Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. Proc Natl Acad Sci U S A 2001;98:8662–7.

Fenteany G, Standaert RF, Lane WS, et al. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science 1995;268:726–31.

Asselin E, Mills GB, Tsang BK. XIAP regulates Akt activity and caspase-3-dependent cleavage during cisplatin-induced apoptosis in human ovarian epithelial cancer cells. Cancer Res 2001;61:1862–8.

Huang H-K, Joazeiro CA, Bonfoco E, et al. The inhibitor of apoptosis, cIAP2, functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of caspase3 and 7. J Biol Chem 2000;275:26661–4.

Deveraux QL, Takahashi R, Salvesen GS, et al. X-linked IAP is a direct inhibitor of cell-death proteases. Nature 1997;388:300–4.

Yang X, Xing H, Gao Q, et al. Regulation of HtrA2/Omi by X-linked inhibitor of apoptosis protein in chemoresistance in human ovarian cancer cells. Gynecol Oncol 2005;97:413–21.

Srinivasula SM, Gupta S, Datta P, et al. Inhibitor of apoptosis proteins are substrates for the mitochondrial serine protease Omi/HtrA2. J Biol Chem 2003;278:31469–72.

Leverkus M, Sprick MR, Wachter T, et al. Proteasome inhibition results in TRAIL sensitization of primary keratinocytes by removing the resistance-mediating block of effector caspase maturation. Mol Cell Biol 2003;23:777–90.

Tenev T, Zachariou A, Wilson R, et al. IAPs are functionally non-equivalent and regulate effector caspases through distinct mechanisms. Nat Cell Biol 2004;7:70–7.

Pandey P, Farber R, Nakazawa A, et al. Hsp27 functions as a negative regulator of cytochrome c-dependent activation of procaspase-3. Oncogene 2000;19:1975–81.

Kamradt MC, Chen F, Cryns VL. The small heat shock protein αB-crystallin negatively regulates cytochrome c- and caspase-8-dependent activation of caspase-3 by inhibiting its autoproteolytic maturation. J Biol Chem 2001;276:16059–63.

Kamradt MC, Lu M, Werner ME, et al. The small heat shock protein αB-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3. J Biol Chem 2005;289:11059–66.

Li J, Feng Q, Kim J-M, et al. Human ovarian cancer and cisplatin resistance: possible role of inhibitor of apoptosis proteins. Endocrinology 2001;142:370–80.

Sasaki H, Sheng YL, Kotsuji F, et al. Down-regulation of X-linked inhibitor of apoptosis protein induces apoptosis in chemoresistant human ovarian cancer cells. Cancer Res 2000;60:5659–66.

Cenni B, Aebi S, Nehmé A, et al. Epidermal growth factor enhances cisplatin-induced apoptosis by a caspase-3 independent pathway. Cancer Chemother Pharmacol 2001;47:397–403.

Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis for resistance. Oncogene 2003;22:7265–79.