Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry , Palacky University , Hnevotinska 5 , 77900 Olomouc , Czech Republic.
School of Biological Sciences and Centre for Biodiscovery , Victoria University of Wellington , Wellington 6012 , New Zealand.
J Nat Prod. 2018 Mar 23;81(3):634-640. doi: 10.1021/acs.jnatprod.7b00961. Epub 2018 Feb 5.
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.
在常氧条件下，HCT116 结直肠癌细胞对佩洛利德 A（PLA）的敏感性不受细胞缺氧预处理的影响。我们研究了在缺氧条件下 PLA 的作用是否发生改变，以及该活性是否依赖于 p53。在野生型 HCT116 细胞中，PLA 的细胞毒性在很大程度上不受缺氧的影响；然而，敲除 p53 的细胞则表现出耐药性。在缺氧条件下，敲除 p21 基因对 PLA 的活性几乎没有影响。结论是，细胞对微管稳定剂 PLA 的反应在缺氧条件下是一个依赖 p53 的过程。
