This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lövborg, H. Articles by Wesierska-Gadek, J. Search for Related Content PubMed PubMed Citation Articles by Lövborg, H. Articles by Wesierska-Gadek, J.

Action of a Novel Anticancer Agent, CHS 828, on Mouse Fibroblasts

Increased Sensitivity of Cells Lacking Poly (ADP-Ribose) Polymerase-1¹

Henrik Lövborg, Jacek Wojciechowski, Rolf Larsson and Józefa Wsierska-Gdek²

Department of Clinical Pharmacology, Uppsala University Hospital, Uppsala, Sweden [H. L., R. L.,] and the Institute of Cancer Research, University of Vienna, Vienna, Austria [J. W., J. W-G.]

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 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.

This article has been cited by other articles:

				M. Watson, A. Roulston, L. Belec, X. Billot, R. Marcellus, D. Bedard, C. Bernier, S. Branchaud, H. Chan, K. Dairi, et al. The Small Molecule GMX1778 Is a Potent Inhibitor of NAD+ Biosynthesis: Strategy for Enhanced Therapy in Nicotinic Acid Phosphoribosyltransferase 1-Deficient Tumors Mol. Cell. Biol., November 1, 2009; 29(21): 5872 - 5888. [Abstract] [Full Text] [PDF]

				K. Meyer, M. Ait-Goughoulte, Z.-Y. Keck, S. Foung, and R. Ray Antibody-Dependent Enhancement of Hepatitis C Virus Infection J. Virol., March 1, 2008; 82(5): 2140 - 2149. [Abstract] [Full Text] [PDF]

				J. Wesierska-Gadek, D. Schloffer, M. Gueorguieva, M. Uhl, and A. Skladanowski Increased Susceptibility of Poly(ADP-Ribose) Polymerase-1 Knockout Cells to Antitumor Triazoloacridone C-1305 Is Associated with Permanent G2 Cell Cycle Arrest Cancer Res., July 1, 2004; 64(13): 4487 - 4497. [Abstract] [Full Text] [PDF]

				W.-P. Lee, D.-I. Tai, S.-L. Tsai, C.-T. Yeh, Y. Chao, S.-D. Lee, and M.-C. Hung Adenovirus Type 5 E1A Sensitizes Hepatocellular Carcinoma Cells to Gemcitabine Cancer Res., October 1, 2003; 63(19): 6229 - 6236. [Abstract] [Full Text] [PDF]