Peloruside A-Induced Cell Death in Hypoxia Is p53 Dependent in HCT116 Colorectal Cancer Cells

J Nat Prod. 2018 Mar 23;81(3):634-640. doi: 10.1021/acs.jnatprod.7b00961. Epub 2018 Feb 5.

Abstract

HCT116 colorectal cancer cell sensitivity to peloruside A (PLA) in normoxia is not altered by hypoxia preconditioning of the cells. We examined whether the PLA effects were altered in hypoxia and whether the activity was dependent on p53. The cytotoxicity of PLA in wild-type HCT116 cells was largely unaffected by hypoxia; however, cells in which p53 was knocked out showed resistance. Knockout of the p21 gene had little effect on the activity of PLA in hypoxia. It was concluded that the response of cells to the microtubule-stabilizing agent PLA under hypoxic conditions is a p53-dependent process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Cell Death / drug effects*
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • HCT116 Cells
  • Humans
  • Hypoxia / drug therapy*
  • Hypoxia / metabolism
  • Lactones / pharmacology*
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Cyclin-Dependent Kinase Inhibitor p21
  • Lactones
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • peloruside A