ABSTRACT
Suppression of resistance to anticancer drugs by COTC of glyoxalase I (GloI) inhibitor targeting intracellular glutathione (GSH) and GloI was studied. Depletion of the cellular GSH content and inhibition of GloI by COTC increased chemotherapy-mediated apoptosis in apoptosis-resistant pancreatic adenocarcinoma AsPC-1 cells.
Subject(s)
Cyclohexanones/chemistry , Drug Resistance, Neoplasm/drug effects , Glutathione/antagonists & inhibitors , Lactoylglutathione Lyase/antagonists & inhibitors , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cyclohexanones/pharmacology , Humans , Pancreatic Neoplasms/pathology , Structure-Activity RelationshipABSTRACT
The novel cyclic hexadepsipeptide named pipalamycin was isolated from a culture filtrate of Streptomyces sp. ML297-90F8 as an apoptosis-inducing agent. The antibiotic was found to be consisting of each one mole of alanine, N-hydroxyalanine, glycine, N-acylated 3-hydroxyleucine, and two moles of piperazic acid. Pipalamycin induced apoptosis in apoptosis-resistant human pancreatic adenocarcinoma AsPC-1 cells at 0.3 microg/ml in 24 to approximately 48 hours. It also showed antibacterial activity on Gram-positive bacteria such as Staphylococcus aureus and Micrococcus luteus. Fermentation, isolation, structural elucidation and the biological activities of pipalamycin are described.
