Anticancer and apoptosis-inducing activities of microbial metabolites

Abstract

The problems of systemic toxicity and drug resistance in cancer chemotherapy urge the continuing discovery of new anticancer agents. We explored the specific anticancer activity from microbial metabolites to find new lead compound. 394 microbial extracts were evaluated on anti-proliferative activity against 4 cancer cell lines using MTT assay. Of these, 20 samples showed varying degree of cytotoxicity but specifically to the cancer cell lines since the growth of normal cells was not significantly inhibited by 1 mg/ml of each cell extracts. The 4 most potent extracts exhibited strongest growth inhibition to each cancer cell type were selected for further studied. Cell morphological changes such as cell shrinkage, lose of surface contact and blebbing were observed in all treated cancer cells. DNA-binding dye staining demonstrated nuclear condensation and fragmentation. Chromosomal DNA cleavage detected as DNA ladder pattern by gel electrophoresis including activation of cellular caspase-3 activity, a hallmark of apoptosis, were observed in all treated cancer cell lines. These characteristics suggested the mechanism of apoptosis cell death induced by the extracts. No growth inhibition and apoptosis characteristic were detected in normal cells even at high concentration used suggesting the selective cytotoxicity and potential candidates to develop as anticancer agents. © 2010 by Pontificia Universidad Católica de Valparaíso, Chile.