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

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.