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.