Inhibition of DNA topoisomerase I and II, and growth inhibition of MDA-MB-231 human breast cancer cells by bis-benzimidazole derivatives with alkylating moiety.

Abstract

The purpose of the present study was to identify the cellular processes and targets affected by treatment with bis-benzimidazole derivatives with chloroalkyl and bromoalkyl moieties (1-4) in the estrogen receptor-negative MDA-MB-231 human breast cancer cells. Treatment of the cells revealed that these compounds inhibited DNA synthesis and irreversibly inhibited the proliferative activity of the cells. All drugs 1-4 inhibited relaxation of pBR 322 DNA induced by both topoisomerases, although topoisomerase I was 2- to 9-fold more sensitive than topoisomerase II. This suggests that DNA-binding may be implicated in the cytotoxicity of bis-benzimidazole derivatives with alkylating moiety, possibly by inhibiting interactions between topoisomerases and their DNA targets.

• Authors: Krzysztof Bielawski, Sławomir Wołczyński, Anna Bielawska
• Journal: Polish journal of pharmacology (Pol J Pharmacol) 2004 May-Jun Vol. 56 Issue 3 Pg. 373-8 ISSN: 1230-6002 [Print] Poland
• PMID: 15215569 (Publication Type: Journal Article)

Chemical References

• Benzimidazoles
• Topoisomerase I Inhibitors
• Topoisomerase II Inhibitors
• DNA

Topics

• Benzimidazoles (pharmacology)
• Breast Neoplasms (metabolism)
• Cell Survival (drug effects)
• DNA (biosynthesis, metabolism)
• Female
• Humans
• Structure-Activity Relationship
• Topoisomerase I Inhibitors
• Topoisomerase II Inhibitors
• Tumor Cells, Cultured