Induction of Apoptosis by Genistein in Human Melanoma Cells / 대한해부학회지

ABSTRACT

Genistein is a naturally occurring isoflavone that has been identified predominantly in soybean. It has been found that genistein can inhibit the growth of various cancer cell lines. Melanoma continues to increase in incidence in many parts of the world and remains among the top six cancers as a cause of death and morbidity. Understanding and overcoming resistance mechanism(s) of melanoma to apoptosis would therefore facilitate identification of new therapeutic targets and development of new treatments. This study was undertaken to investigate whether genistein induced apoptosis on human melanoma cells (G361). Genistein had a significant dose- and time-dependent inhibitory effect on the viability of G361 cells. The death of cells was further demonstrated to be due to apoptosis characterized by chromatin condensation and apoptotic bodies by hoechst staining, and DNA electrophoresis. p53 levels were not altered by genistein treatment. Genistein treatment induced caspase-3 cleavage and activation. Poly (ADP-ribose)-polymerase (PARP) and DNA fragmentation factor 45 (DFF45), which are caspase-3 substrates, were cleaved during genistein-induced apoptosis. It was found that the caspase-6 substrate lamin A was cleaved, whose cleavage has been reported to be necessary for complete condensation of DNA during apoptosis. The expression level and phosphorylation of focal adhesion kinase (FAK) were reduced by genistein treatment. These results suggest that genistein may constitute a potential antitumor compound against melanoma occurring at oral mucosa and skin.