Abstract
The newly synthesized calcium channel blocker, Ro44-5912, significantly potentiates doxorubicin (Dox)-induced cytotoxicity at non-cytotoxic concentrations in Dox-resistant human ovarian cell line, A2780/DX5, overexpressing P170-glycoprotein (Pgp). Induction of DNA single- and double-strand breaks (ssbs and dsbs) was measured using alkaline elution and constant-field gel electrophoresis (CFGE) assays. The results indicate that potentiation of the cytotoxicity of Dox by Ro44-5912 was accompanied by significant increases in both, Dox-induced DNA ssbs and dsbs in the resistant cells. Pulsed-field gel electrophoresis (PFGE) analysis showed that Dox induced DNA fragments in the 50-800 kilobase (kb) and 0.8-5.7 megabase (Mb) ranges. The majority of the newly synthesized DNA fragments were in the 50-800 kb range. Ro44-5912 treatment resulted in significant potentiation of DNA fragmentation in the 50-800 kb range with a minor increase in 0.8-5.7 Mb DNA fragments, suggesting that the modulator functions by potentiating nascent DNA fragmentation in the resistant cells. Exposure to Dox with Ro44-5912 was associated with a prolonged blockage of cells in the S-phase. In contrast, exposure to Dox alone resulted in temporary blockage of cells ...Continue Reading
References
Mar 1, 1992·International Journal of Radiation Biology·G IliakisM Jackson
Dec 4, 1992·Science·S P ColeR G Deeley
Feb 14, 1992·Biochemical and Biophysical Research Communications·F ZindyC Bréchot
Apr 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J RosenblattD O Morgan
Jan 1, 1992·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·S J Whitaker
Jun 1, 1991·Mutation Research·A J GiacciaJ M Brown
Dec 20, 1991·Cell·F GirardN J Lamb
Jan 29, 1991·Biochemistry·D H Sorscher, M Cordeiro-Stone
Jul 4, 1990·Journal of the National Cancer Institute·P SkehanM R Boyd
Jan 1, 1989·Annual Review of Biochemistry·L F Liu
Jan 1, 1989·Annual Review of Biochemistry·J A Endicott, V Ling
Jan 1, 1989·Cancer Chemotherapy and Pharmacology·M A Alaoui JamaliY M Rustum
Jun 1, 1984·Science·A M RoganR F Ozols
May 1, 1984·Cell·D C Schwartz, C R Cantor
May 18, 1984·Science·M A GoldmanA Nag
May 4, 1995·International Journal of Cancer. Journal International Du Cancer·Y H LingR Perez-Soler
Jan 1, 1993·Annual Review of Biochemistry·M M Gottesman, I Pastan
May 1, 1994·Carcinogenesis·A J RyanR T Johnson
Jan 1, 1993·Advances in Cancer Research·K V ChinM M Gottesman
Citations
May 3, 2003·Journal of Experimental Therapeutics & Oncology·John A Kellen
Aug 2, 2002·Biochemical and Biophysical Research Communications·Ming-biao YinYoucef M Rustum
Oct 23, 2013·PloS One·Yvonne K GirardSubhra Mohapatra