This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, Z. Articles by Tsuruo, T. Search for Related Content PubMed PubMed Citation Articles by Chen, Z. Articles by Tsuruo, T.

Activation of Actin-cleavable Interleukin 1ß-converting Enzyme (ICE) Family Protease CPP-32 during Chemotherapeutic Agent-induced Apoptosis in Ovarian Carcinoma Cells¹

Laboratory of Biomedical Research, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113 [Z. C., M. N., T. M., T. T.], and Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1, Kami-Ikebukuro, Toshima-ku, Tokyo 170 [T. T.], Japan

We have previously reported that actin cleavage activity (ACA) by interleukin 1ß-converting enzyme (ICE) family protease was elevated during anticancer drug-induced apoptosis in human leukemia U937 cells. In this study, the involvement of ACA in the drug-induced apoptosis in solid tumor cells was investigated. Human ovarian carcinoma OVCAR-3 cells undergo apoptotic cell death when cells are treated with chemotherapeutic agents such as cisplatin and etoposide. The induction of the actin cleavage activity accompanied the development of apoptosis. ICE/ced-3 family protease inhibitors such as Z-VAD-CH₂DCB and Z-EVD-CH₂DCB at 100 µg/ml prevented both the emergence of ACA and the morphological change, characteristics of apoptosis, in cisplatin-treated OVCAR-3 cells. The ACA in apoptotic OVCAR-3 cell lysate was greatly adsorbed by antibody against CPP-32, an ICE family protease. Furthermore, the immunoprecipitated CPP-32 from OVCAR-3 lysate could cleave actin to generate a 15-kDa fragment, as did the apoptotic OVCAR-3 cell lysate, indicating that CPP-32 is a major protease responsible for the ACA. The activation of CPP-32 in the drug-treated cell lysate was verified with Western blot analysis. Our present results indicate that CPP-32, an actin cleavage ICE/ced-3 family protease, could be a common mediator involved in the process of chemotherapy-induced apoptosis of cancer cells.

¹ This study was supported in part by grants from the Ministry of Education, Science and Culture, Japan and the Special Coordination Fund of the Science and Technology Agency, Japan.

² To whom requests for reprints should be addressed.

Received 7/18/96. Accepted 9/19/96.

This article has been cited by other articles:

				K. Stahnke, S. Fulda, C. Friesen, G. Strau{beta}, and K.-M. Debatin Activation of apoptosis pathways in peripheral blood lymphocytes by in vivo chemotherapy Blood, November 15, 2001; 98(10): 3066 - 3073. [Abstract] [Full Text] [PDF]

				A. Biroccio, B. Benassi, S. Amodei, C. Gabellini, D. Del Bufalo, and G. Zupi C-Myc Down-Regulation Increases Susceptibility to Cisplatin through Reactive Oxygen Species-Mediated Apoptosis in M14 Human Melanoma Cells Mol. Pharmacol., July 1, 2001; 60(1): 174 - 182. [Abstract] [Full Text]

				S. R. White, P. Williams, K. R. Wojcik, S. Sun, P. S. Hiemstra, K. F. Rabe, and D. R. Dorscheid Initiation of Apoptosis by Actin Cytoskeletal Derangement in Human Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., March 1, 2001; 24(3): 282 - 294. [Abstract] [Full Text] [PDF]

				E. Asselin, G. B. Mills, and B. K. Tsang XIAP Regulates Akt Activity and Caspase-3-dependent Cleavage during Cisplatin-induced Apoptosis in Human Ovarian Epithelial Cancer Cells Cancer Res., March 1, 2001; 61(5): 1862 - 1868. [Abstract] [Full Text]

				H. Sasaki, Y. Sheng, F. Kotsuji, and B. K. Tsang Down-Regulation of X-linked Inhibitor of Apoptosis Protein Induces Apoptosis in Chemoresistant Human Ovarian Cancer Cells Cancer Res., October 1, 2000; 60(20): 5659 - 5666. [Abstract] [Full Text]

				A. Nakashio, N. Fujita, S. Rokudai, S. Sato, and T. Tsuruo Prevention of Phosphatidylinositol 3'-Kinase-Akt Survival Signaling Pathway during Topotecan-induced Apoptosis Cancer Res., September 1, 2000; 60(18): 5303 - 5309. [Abstract] [Full Text]

				W Bursch, K Hochegger, L Torok, B Marian, A Ellinger, and R. Hermann Autophagic and apoptotic types of programmed cell death exhibit different fates of cytoskeletal filaments J. Cell Sci., January 4, 2000; 113(7): 1189 - 1198. [Abstract] [PDF]

				S. Wesselborg, I. H. Engels, E. Rossmann, M. Los, and K. Schulze-Osthoff Anticancer Drugs Induce Caspase-8/FLICE Activation and Apoptosis in the Absence of CD95 Receptor/Ligand Interaction Blood, May 1, 1999; 93(9): 3053 - 3063. [Abstract] [Full Text] [PDF]

				S. C. Posey and B. E. Bierer Actin Stabilization by Jasplakinolide Enhances Apoptosis Induced by Cytokine Deprivation J. Biol. Chem., February 12, 1999; 274(7): 4259 - 4265. [Abstract] [Full Text] [PDF]

				P. A. JANMEY The Cytoskeleton and Cell Signaling: Component Localization and Mechanical Coupling Physiol Rev, July 1, 1998; 78(3): 763 - 781. [Abstract] [Full Text] [PDF]