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Involvement of oxidative stress and caspase activation in paclitaxel-induced apoptosis of primary effusion lymphoma cells

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Abstract

Paclitaxel has significant antitumor activity in several human tumors, including Kaposi’s sarcoma (KS). Human herpesvirus 8 (HHV-8) is implicated in all forms of Kaposi’s sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD), indicating that it is a DNA tumor virus. Since it is difficult to culture cell lines derived from KS patients, we used a cell line derived from PEL (BCBL-1) to investigate whether oxidative stress is involved in the cytotoxicity of paclitaxel on the HHV-8-related tumors. We found that the generation of reactive oxygen species (ROS) in the BCBL-1 cells was increased by paclitaxel treatment, and the increase in ROS production was suppressed by antioxidants, including catalase and ascorbic acid. Moreover, ascorbic acid also attenuated the cytotoxicity induced by paclitaxel. Upon paclitaxel treatment, caspase-2, caspase-3, and caspase-8 were activated in BCBL-1 cells. Cotreatment with antioxidants did not affect caspase-2, caspase-3 or caspase-8 activation. Paclitaxel-induced apoptosis was also accompanied by an increase in the protein levels of Bax, and this effect was attenuated by antioxidants. Paclitaxel slightly decreased the expression of Bcl-2 protein, but antioxidants induced Bcl-2 protein. These results suggest that oxidative stress is only partially involved in the cytotoxicity of paclitaxel in BCBL-1 cells, and that paclitaxel-induced apoptosis of BCBL-1 cells is primarily mediated by the caspase activation pathway.

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Acknowledgements

This work was partially supported by Fooyin University grant FY-91-015. We would like to thank Dr. Gary R. Whittaker for proofreading the manuscript.

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Authors and Affiliations

  1. Department of Medical Technology, Fooyin University, 151 Chin-Hsuen Road, Ta-Liao, Kaohsiung Hsien, Taiwan, ROC

    Yi-Fen Wang, Chang-Yu Chen, Su-Fang Chung & Horng-Ren Lo

  2. Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC

    Yee-Hsuan Chiou

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  1. Yi-Fen Wang
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Correspondence to Yi-Fen Wang.

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Wang, YF., Chen, CY., Chung, SF. et al. Involvement of oxidative stress and caspase activation in paclitaxel-induced apoptosis of primary effusion lymphoma cells. Cancer Chemother Pharmacol 54, 322–330 (2004). https://doi.org/10.1007/s00280-004-0831-0

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  • DOI: https://doi.org/10.1007/s00280-004-0831-0

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