Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2

Molecular Cancer Therapeutics - Tập 6 Số 2 - Trang 752-761 - 2007
Nizar M. Mhaidat1, Yufang Wang2, Kelly A. Kiejda2, Xu Dong Zhang2, Peter Hersey2
1Immunology and Oncology Unit, Royal Newcastle Hospital, Room 443, David Maddison Clinical Sciences Building, Corner King and Watt Streets, Newcastle, NSW 2300, Australia.
2Immunology and Oncology Unit, Newcastle Misericordiae Hospital, Newcastle, New South Wales, Australia

Tóm tắt

Abstract Taxanes have a broad spectrum of activity against various human cancers, including melanoma. In this study, we have examined the molecular mechanism of docetaxel-induced apoptosis of human melanoma. We report that docetaxel induced varying degrees of apoptosis in a panel of melanoma cell lines but not in normal fibroblasts. Induction of apoptosis was caspase dependent and associated with changes in mitochondrial membrane potential that could be inhibited by overexpression of Bcl-2. Docetaxel induced changes in Bax that correlated with sensitivity to docetaxel-induced apoptosis. These changes in Bax were not inhibited by overexpression of Bcl-2. Kinetic studies of caspase-2 activation by Western blotting and fluorogenic assays revealed that activation of caspase-2 seemed to be the initiating event. Inhibition of caspase-2 with z-VDVAD-fmk or by small interfering RNA knockdown inhibited changes in Bax and mitochondrial membrane potential and events downstream of mitochondria. Activation of caspase-8 and Bid seemed to be a late event, and docetaxel was able to induce apoptosis in cells deficient in caspase-8 and Bid. p53 did not seem to be involved as a p53 null cell line was sensitive to docetaxel and an inhibitor of p53 did not inhibit apoptosis. Small interfering RNA knockdown of PUMA and Noxa also did not inhibit apoptosis. These results suggest that docetaxel induces apoptosis in melanoma cells by pathways that are dependent on activation of caspase-2, which initiates mitochondrial dependent apoptosis by direct or indirect activation of Bax. [Mol Cancer Ther 2007;6(2):752–61]

Từ khóa


Tài liệu tham khảo

Soengas MS, Lowe SW. Apoptosis and melanoma chemoresistance. Oncogene 2003; 22: 3138–51.

Hersey P, Zhang X. How melanoma cells evade TRAIL-induced apoptosis. Nat Rev Cancer 2001;1:142–50.

Hersey P, Zhang XD. Overcoming resistance of cancer cells to apoptosis. J Cell Physiol 2003;196:9–18.

Debatin KM, Poncet D, Kroemer G. Chemotherapy: targeting the mitochondrial cell death pathway. Oncogene 2002;21:8786–803.

Lewanski CR, Gullick WJ. Radiotherapy and cellular signalling. Lancet Oncol 2001;2:366–70.

Wesselborg S, Engels IH, Rossmann E, Los M, Schulze-Osthoff K. Anticancer drugs induce caspase-8/FLICE activation and apoptosis in the absence of CD965 receptor/ligand interaction. Blood 1999;93:3053–63.

Rowinsky EK, Donehower RC. The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics. Pharmacol Ther 1991;52:35–84.

Goncalves A, Braguer D, Carles G, Andre N, Prevot C, Briand C. Caspase-8 activation independent of CD95/CD95-L interaction during paclitaxel-induced apoptosis in human colon cancer cells (HT29-D4). Biochem Pharmacol 2000;60:1579–84.

Bhalla KN. Microtubule-targeted anticancer agents and apoptosis. Oncogene 2003;22:9075–85.

Gogas H, Bafaloukos D, Bedikian AY. The role of taxanes in the treatment of metastatic melanoma. Melanoma Res 2004;14:415–20.

Rao RD, Holtan SG, Ingle JN, et al. Combination of paclitaxel and carboplatin as second-line therapy for patients with metastatic melanoma. Cancer 2006;106:375–82.

Liu X, Kim CN, Yang J, Jemmerson R, Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 1996;86:145–57.

Susin SA, Lorenzo HK, Zamzami N, et al. Mitochondrial release of caspase-2 and -9 during the apoptotic process. J Exp Med 1999;189:381–93.

Du C, Fang M, Li Y, Li L, Wang X. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 2000;102:33–42.

Verhagen AM, Ekert PG, Pakusch M, et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 2000;102:43–53.

Hegde R, Srinivasula SM, Zhang Z, et al. Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J Biol Chem 2002;277:432–8.

Cheng EH, Wei MC, Weiler S. BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell 2001;8:705–11.

Bouillet P, Strasser A. BH3-only proteins—evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death. J Cell Sci 2002;115:1567–74.

von Haefen C, Wieder T, Essmann F, Schulze-Osthoff K, Dorken B, Daniel PT. Paclitaxel-induced apoptosis in BJAB cells proceeds via death receptor-independent, caspase-3/8-driven mitochondrial amplification loop. Oncogene 2003;22:2236–47.

Park SJ, Wu CH, Gordon JD, Zhong X, Emami A, Safa AR. Taxol induces caspase-10-dependent apoptosis. J Biol Chem 2004;279:51057–67.

Zhang XD, Borrow JM, Zhang XY, Nguyen T, Hersey P. Activation of ERK1/2 protects melanoma cells from TRAIL-induced apoptosis by inhibiting Smac/DIABLO release from mitochondria. Oncogene 2003;22:2869–81.

Zhang XD, Zhang XY, Gray CP, Nguyen T, Hersey P. Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of human melanoma is regulated by Smac/DIABLO release from mitochondria. Cancer Res 2001;61:7339–48.

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

Komarov PG, Komarova EA, Kondratov RV, et al. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 1999;285:1733–7.

Li R, Moudgil T, Ross HJ, Hu HM. Apoptosis of non-small-cell lung cancer cell lines after paclitaxel treatment involves the BH3-only proapoptotic protein Bim. Cell Death Differ 2005;12:292–303.

Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not Bcl-X. Cell 1996;87:619–28.

Georgoulias V. Doectaxel (Taxotere) in the treatment of non-small cell lung cancer. Curr Med Chem 2002;9:869–77.

Johnson DE, Gastman BR, Wieckowski E, et al. Inhibitor of apoptosis protein hILP undergoes caspase-mediated cleavage during T lymphocyte apoptosis. Cancer Res 2000;60:1818–23.

Lassus P, Optiz-Araya X, Lazebnik Y. Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization. Science 2002;297:1352–4.

Robertson JD, Enoksson M, Suomela M, Zhivotovsky B, Orrenius S. Caspase-2 acts upstream of mitochondria to promote cytochrome c release during etoposide-induced apoptosis. J Biol Chem 2002;277:29803–9.

Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES. Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria. J Biol Chem 2002;277:13430–7.

Nihal M, Ahmad N, Mukhtar H, Wood GS. Anti-proliferative and proapoptotic effects of (−)-epigallocatechin-3-gallate on human melanoma: possible implications for the chemoprevention of melanoma. Int J Cancer 2005;114:513–21.

Hsu YT, Youle RT. Bax in murine thymus is soluble monomeric protein that displays differential detergent-induced conformations. J Biol Chem 1998;273:10777–83.

Griffiths GJ, Dubrez L, Morgan CP, et al. Cell damage-induced conformational changes of the pro-apoptotic protein Bak in vivo precede the onset of apoptosis. J Cell Biol 1999;144:903–14.

Dewson G, Snowden RT, Almond JB, Dyer MJ, Cohen GM. Conformational changes and mitochondrial translocation of Bax accompany proteasome inhibitor-induced apoptosis of chronic lymphocytic leukemia cells. Oncogene 2003;22:2643–54.

Tinel A, Tschopp J. The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science 2004;304:843–6.

Harvey NL, Butt AJ, Kumar S. Functional activation of Nedd2/ICH-1 (caspase-2) is an early process in apoptosis. J Biol Chem 1997;272:13134–9.

Duan H, Dixit VM. RAIDD is a new “death” adaptor molecule. Nature 1997;385:86–9.

Ahmad M, Seinivasula SM, Wang L, et al. CRADD, a novel human apoptotic adaptor molecule for caspase-2, and FasL/tumor necrosis factor receptor-interacting protein RIP. Cancer Res 1997;57:615–9.

Lavrik IN, Golks A, Baumann S, Krammer PH. Caspase-2 is activated at the CD95 death-inducing signaling complex in the course of CD95-induced apoptosis. Blood 2006;108:559–65.

Paroni G, Henderson C, Schneider C, Brancolini C. Caspase-2 can trigger cytochrome c release and apoptosis from the nucleus. J Biol Chem 2002;277:15147–61.

Sawada M, Hayes P, Matsuyama S. Cytoprotective membrane-permeable peptides designed from Bax-binding domain of Ku70. Nat Cell Biol 2003;5:352–7.

Guo B, Zhai D, Cabezas E, et al. Human peptide suppresses apoptosis by interfering with Bax activation. Nature 2003;423:456–61.

Zhang XD, Wu JJ, Gillespie SK, Borrow JM, Hersey P. Human melanoma cells selected for resistance to apoptosis by prolonged exposure to TRAIL are more vulnerable to necrotic cell death induced by Cisplatin. Clin Cancer Res 2006;12:1355–64.

Thông tin
Thông tin xuất bản

Molecular Cancer Therapeutics

Tập 6 Số 2

752-761

Thông tin tác giả