Cellular Responses to the DNA Damaging Natural Compound Leinamycin
1Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA
2Departments of Chemistry and Biochemistry, University of Missouri, Columbia, MO 65211, USA
- *Corresponding Author:
- Daekyu Sun, PhD
Department of Pharmacology and Toxicology
College of Pharmacy, University of Arizona
BIO5 Institute, Room 102,1657 E. Helen Street
Tucson, Arizona 85721, USA
Tel: (520) 626-0323
Fax: (520) 626-4824
E-mail: [email protected]
Received Date: March 28, 2012; Accepted Date: May 09, 2012; Published Date: May 11, 2012
Citation: Sinha P, Shin Y, Hays AM, Gates K, Sun D (2012) Cellular Responses to the DNA Damaging Natural Compound Leinamycin. J Cancer Sci Ther S8:003. doi: 10.4172/1948-5956.S8-003
Copyright: © 2012 Sinha P, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Leinamycin is a thiol dependent DNA alkylating agent which shows very potent activity against various human cancer cell lines (IC50 values in the low nanomolar range). This natural compound forms guanine adducts (N7) in DNA which are converted into abasic sites and simultaneously generates Reactive Oxygen Species (ROS), to produce DNA strand breaks in human cancer cells. Our present study shows that leinamycin induces a group of DNA repair and transcription factor genes involved in DNA repair in a MDA-MB-231 human breast cancer cell line, which can mediate chemoresistance to leinamycin. In addition, N-acetylcysteine decreases leinamycin-mediated ROS production while increasing leinamycin mediated apoptotic cell death, without affecting the induction of repair genes. These data indicate that ROS is not a crucial player in leinamycin induced DNA damage and that a precursor of glutathione, N-acetylcysteine, can potentiate leinamycin mediated cytotoxicity by increasing the activation of leinamycin into its DNA reactive form.