Chelerythrine induces reactive oxygen species-dependent mitochondrial apoptotic pathway in a murine T cell lymphoma

Abstract

Chelerythrine is a well-known protein kinase C inhibitor and potential antiproliferative and antitumor pharmacological agent. Chelerythrine inhibits/suppresses the HSF1 phosphorylation by inhibiting PKC and blocks the nuclear migration and subsequent synthesis of hsp70 leading to reduced cell viability and activation of apoptotic machinery. Chelerythrine is also known to enhance the production of reactive oxygen intermediate that is strong activator of apoptosis in high concentration. Therefore, the present study intended to investigate the role of chelerythrine-induced reactive oxygen intermediate on the viability and apoptosis of Dalton's lymphoma cells. Enhanced production of reactive oxygen species in Dalton's lymphoma (DL) cells was observed upon treatment of chelerythrine only which was seen completely abolished on treatment of mitochondrial complex inhibitors rotenone and malonate, and anti-oxidant, N-acetyl-L-cysteine. Increased number of DL cells undergoing apoptosis, as observed by fluorescent microscopy and flow cytometry analysis, in chelerythrine only-treated group was seen that was significantly inhibited on treatment of mitochondrial complex inhibitors and anti-oxidants. Staurosporine, on the other hand, does not lead to enhanced production of reactive oxygen intermediate in DL cells.