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. 2002 Aug 1;62(15):4206-11.

Action of a novel anticancer agent, CHS 828, on mouse fibroblasts: increased sensitivity of cells lacking poly (ADP-Ribose) polymerase-1

Henrik Lövborg  1 , Jacek Wojciechowski, Rolf Larsson, Józefa Wesierska-Gadek
Affiliations
  • PMID: 12154020

Action of a novel anticancer agent, CHS 828, on mouse fibroblasts: increased sensitivity of cells lacking poly (ADP-Ribose) polymerase-1

Henrik Lövborg et al. Cancer Res. .

Abstract

We observed stronger cytotoxic effect of CHS 828 on poly(ADP-ribose) polymerase-1(PARP-1) knock-out cells as compared with the normal counterpart. The proliferation of PARP-1 -/- cells was inhibited by a drug concentration approximately 3-fold lower than that in the normal cells. The monitoring of p53 levels revealed that CHS 828 induced p53 response in a dose-dependent manner in only normal cells. The drug, however, failed to activate the p53 protein in PARP-1-deficient cells even after combined treatment with multidrug-resistant modulators. These results show that the PARP-1 inactivation sensitizes cells to the novel anticancer drug CHS 828 and that the drug is able to activate different cellular pathways depending on PARP-1 status.

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