Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis
- 1 January 1996
- journal article
- Published by Springer Nature in Nature Medicine
- Vol. 2 (1) , 72-79
- https://doi.org/10.1038/nm0196-72
Abstract
The anticancer agent paclitaxel (Taxol) stabilizes tubulin polymerization resulting in arrest in mitosis and apoptotic cell death. Normal human fibroblasts depleted of functional p53 by SV40 T antigen or HPV-16 E6, and primary embryo fibroblasts from p53 null mice showed seven- to ninefold increased cytotoxicity by paclitaxel. Reduced levels of p53 correlated with increased G2/M phase arrest, micronucleation, and p53-independent paclitaxel-induced apoptosis. Surviving cells with intact p53 progressed through mitosis and transiently accumulated in the subsequent G1 phase, coincident with increased p53 and p21cip1,waf1 protein levels. These results are in contrast to studies linking p53 loss with resistance to DNA damaging anticancer agents.Keywords
This publication has 34 references indexed in Scilit:
- Cytotoxicity of the anticancer agents cisplatin and taxol during cell proliferation and the cell cycleInternational Journal of Cancer, 1994
- Differential disruption of genomic integrity and cell cycle regulation in normal human fibroblasts by the HPV oncoproteins.Genes & Development, 1994
- WAF1, a potential mediator of p53 tumor suppressionCell, 1993
- Thymocyte apoptosis induced by p53-dependent and independent pathwaysNature, 1993
- p53 is required for radiation-induced apoptosis in mouse thymocytesNature, 1993
- Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumoursNature, 1992
- A deadly inheritanceNature, 1990
- Shared Actions of Endotoxin and Taxol on TNF Receptors and TNF releaseScience, 1990
- Association of Human Papillomavirus Types 16 and 18 E6 Proteins with p53Science, 1990
- Microtubule stabilization by taxol inhibits initiation of DNA synthesis by thrombin and by epidermal growth factorCell, 1981