title: Involvement of caspase activation and mitochondrial stress in taxol-induced apoptosis of Epstein-Barr virus-infected Akata cells.
abstract: Taxol (paclitaxel) is one of the most potent antimicrotubule agents currently used in cancer chemoprevention and treatment. However, the effects of taxol on the induction of apoptosis in Epstein-Barr virus (EBV)-infected cells are unknown. This study investigated the mechanisms of taxol on cell cycle arrest and apoptosis induction using the EBV-infected cell line, Akata. Taxol treatment sensitively and dose-independently induced growth inhibition, cytotoxicity, and apoptosis in the cells, which was demonstrated by the decreased level of tritium incorporation and cell viability, the increased number of positively stained cells in the trypan blue staining and TUNEL assay, the increased population of cells in the sub-G(0)/G(1) phase in flow cytometric analysis, and ladder formation of the genomic DNA. Treatment with z-VAD-fmk almost completely protected the cells from taxol-induced apoptosis indicating that the taxol-induced apoptosis of Akata cells is caspase-dependent. In addition, taxol-induced apoptosis is proposed to be associated with a lower mitochondrial membrane potential and G(2)/M arrest. However, the tubulin expression level doses not appear to be a direct mediator of taxol-induced apoptosis in cells. The presence of EBV in these cells was not related to the sensitivity of the cells to the induction of apoptosis by taxol. Overall, these results demonstrate that taxol induces apoptosis in EBV-infected Akata cells in a dose-independent manner, and that caspase activation and mitochondrial stress are involved in the induction.
authors.affiliation: Laboratory of Cell Biology in Department of Orthodontics, Institute of Oral Biosciences and The Research Center of Bioactive Materials, Chonbuk National University, Chonju, Korea.
authors.forename: Young-Ok
authors.initials: YO
authors.lastname: Son
authors.forename: Ki-Choon
authors.initials: KC
authors.lastname: Choi
authors.forename: Jeong-Chae
authors.initials: JC
authors.lastname: Lee
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Kook
authors.forename: Suk-Kyeong
authors.initials: SK
authors.lastname: Lee
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takada
authors.forename: Yong-Suk
authors.initials: YS
authors.lastname: Jang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D004789:Enzyme Activation; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D020287:In Situ Nick-End Labeling; D008564:Membrane Potentials; D008928:Mitochondria / Q000187:drug effects*; D017239:Paclitaxel / Q000494:pharmacology*
chemical_list: D020169:Caspases; D017239:Paclitaxel