1. Academic Validation
  2. Taxol-induced growth arrest and apoptosis is associated with the upregulation of the Cdk inhibitor, p21WAF1/CIP1, in human breast cancer cells

Taxol-induced growth arrest and apoptosis is associated with the upregulation of the Cdk inhibitor, p21WAF1/CIP1, in human breast cancer cells

  • Oncol Rep. 2012 Dec;28(6):2163-9. doi: 10.3892/or.2012.2060.
Yung Hyun Choi 1 Young Hyun Yoo
Affiliations

Affiliation

  • 1 Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea. [email protected]
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.

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