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Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis

Nature Medicine volume 2, pages 72–79 (1996)Cite this article

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.

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Authors and Affiliations

  1. Bristol-Myers Squibb Pharmaceutical Research Institute, 3005 First Avenue, Seattle, Washington, 98121, USA

    Alan F. Wahl & Karen L. Donaldson

  2. Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, New Jersey, 08543, USA

    Craig Faircnild & Frank Y.F. Lee

  3. Fred Hutchinson Cancer Research Center, Cancer Biology Program, 1124 Columbia Street #C1-015, Seattle, Washington, 98104, USA

    Scott A. Foster, G. William Demers & Denise A. Galloway

Authors
  1. Alan F. Wahl
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  3. Craig Faircnild
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  5. Scott A. Foster
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Wahl, A., Donaldson, K., Faircnild, C. et al. Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis. Nat Med 2, 72–79 (1996). https://doi.org/10.1038/nm0196-72

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