Enhancement of non-homologous end joining DNA repair capacity confers cancer cells resistance to the novel selenophene compound, D-501036.

Abstract

D-501036 is a promising anti-cancer compound that exhibits potent anti-proliferative activity against various types of human cancers through the induction of double strand DNA breaks. To determine drug resistance mechanism related to this class of DNA-damaging agents, a KB-derived D-501036-resistant cell line (S4) was established. Results showed that S4 cells exhibit enhanced DNA rejoining ability as compare to KB cells, through up-regulation of the non-homologous end joining activity. In conclusion, enhancement of NHEJ activity plays important role in the development of D-501036-resistance and targeting NHEJ-related molecules maybe able to overcome drug resistance to DNA damaging agents.

• Authors: Yung-Ning Yang, Kai-ming Chou, Wen-Yu Pan, Yih-wen Chen, Tsui-Chun Tsou, Ssu-Ching Yeh, Chun Hei Antonio Cheung, Li-Tzong Chen, Jang-Yang Chang
• Journal: Cancer letters (Cancer Lett) Vol. 309 Issue 1 Pg. 110-8 (Oct 01 2011) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 21684680 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 2,5-bis(5-hydroxymethyl-2-selenienyl)-3-hydroxymethyl-N-methylpyrrole
• Antineoplastic Agents
• Organoselenium Compounds
• Pyrroles

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Cell Line, Tumor
• DNA Breaks, Double-Stranded
• DNA Repair (genetics)
• Drug Resistance, Neoplasm (genetics)
• Female
• Humans
• Organoselenium Compounds (pharmacology, therapeutic use)
• Pyrroles (pharmacology, therapeutic use)
• Up-Regulation
• Uterine Cervical Neoplasms (drug therapy, genetics, metabolism, pathology)