Involvement of oxidative stress and caspase activation in paclitaxel-induced apoptosis of primary effusion lymphoma cells.
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.
Wang
Yi-Fen
YF
Department of Medical Technology, Fooyin University, 151 Chin-Hsuen Road, Ta-Liao, Kaohsiung Hsien, Taiwan, ROC. yfwang@mail.fy.edu.tw
Chen
Chang-Yu
CY
Chung
Su-Fang
SF
Chiou
Yee-Hsuan
YH
Lo
Horng-Ren
HR
D000975:Antioxidants; D053143:Caspase 2; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D004789:Enzyme Activation; D006801:Humans; D018384:Oxidative Stress; D017239:Paclitaxel / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D017382:Reactive Oxygen Species; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053143:Caspase 2; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases; D017239:Paclitaxel