title: Taxol-induced growth arrest and apoptosis is associated with the upregulation             of the Cdk inhibitor, p21WAF1/CIP1, in human breast cancer cells.
abstract: The anticancer agent, taxol, stabilizes tubulin polymerization, resulting             in arrest at the G2/M phase of the cell cycle and apoptotic cell death. However,             the molecular mechanism of this growth inhibition and apoptosis is poorly understood.             In this study, we used MCF-7 and MDA-MB-231 human breast carcinoma cells which             have different estrogen receptor (ER) and tumor suppressor p53 statuses to examine             the mechanisms of taxol-induced growth inhibition and apoptosis. Treatment of             the cells with taxol resulted in a time-dependent inhibition of cell viability,             which was accompanied by an accumulation of cells at G2/M and the sub-G1 apoptotic             region, determined by flow cytometric analysis. Furthermore, chromatin condensation,             DNA ladder formation and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP)             in both cell lines were observed following treatment with taxol, indicating the             occurrence of apoptotic cell death. Western blot analysis using whole cell lysates             from MCF-7 and MDA-MB-231 cells treated with taxol demonstrated that taxol treatment             inhibited expression of cyclin A and cyclin B1 proteins in a time-dependent manner.             The inhibitory effects of taxol on cell growth and apoptosis induced by taxol             were also associated with the downregulation of Wee1 kinase expression and a marked             induction in the activity of the cyclin-dependent kinase inhibitor, p21WAF/CIP1.             Furthermore, taxol elevated p21 promoter activity in both cell lines. These findings             suggest that taxol-induced G2/M arrest and apoptosis in human breast carcinoma             cells is mediated through the ER- and p53-independent upregulation of p21.
authors.affiliation: Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea. choiyh@deu.ac.kr
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019925:Cyclin A / Q000096:biosynthesis; D056744:Cyclin B1 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019925:Cyclin A; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009687:Nuclear Proteins; D011065:Poly(ADP-ribose) Polymerases; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D017239:Paclitaxel