ABSTRACT
Epo-C12 is a synthetic derivative of epolactaene, isolated from Penicillium sp. BM 1689-P. Epo-C12 induces apoptosis in human acute lymphoblastoid leukemia BALL-1 cells. In our previous studies, seven proteins that bind to Epo-C12 were identified by a combination of pull-down experiments using biotinylated Epo-C12 (Bio-Epo-C12) and mass spectrometry. In the present study, the effect of Epo-C12 on peroxiredoxin 1 (Prx 1), one of the proteins that binds to Epo-C12, was investigated. Epo-C12 inhibited Prx 1 peroxidase activity. However, it did not suppress its chaperone activity. Binding experiments between Bio-Epo-C12 and point-mutated Prx 1s suggest that Epo-C12 binds to Cys52 and Cys83 in Prx 1. The present study revealed that Prx 1 is one of the target proteins through which Epo-C12 exerts an apoptotic effect in BALL-1 cells.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Peroxiredoxins/antagonists & inhibitors , Animals , Antineoplastic Agents/chemistry , Cell Line, Tumor , Enzyme Inhibitors , Epoxy Compounds/chemistry , Gene Expression Regulation, Enzymologic/drug effects , Humans , Molecular Structure , Mutation , Peroxiredoxins/genetics , Peroxiredoxins/metabolism , Polyenes/chemistryABSTRACT
Epolactaene, isolated from cultured Penicillium sp. BM 1689-P mycelium, induces neurite outgrowth and arrests the cell cycle of the human neuroblastoma cell line, SH-SY5Y, at the G1 phase. We have found that epolactaene and its derivatives induce apoptosis in the human leukemia B-cell line, BALL-1. In this study, we prepared fluorescent and biotinylated epolactaene derivatives. We characterized the cellular location and the identification of BALL-1 proteins that reacted with these compounds. The results obtained from the reaction of epolactaene or its derivative with N-acetylcysteine methyl ester indicate that these compounds induce the disulfide formation and the alpha-position of the epoxylactam core is the reactive site.
