Anti-proliferative effect of clitocine from the mushroom Leucopaxillus giganteus on human cervical cancer HeLa cells by inducing apoptosis

Clitocine, a natural biologically active substance isolated from the mushroom Leucopaxillus giganteus, possesses several bioactivities including antitumor. Here, for the first time, we studied the molecular mechanism of clitocine-induced apoptosis in human cervical cancer cells (HeLa). Clitocine-induced cell death was characterized with the changes in cell morphology, DNA fragmentation, activation of caspase-3, -8, and -9 (like) activities, poly(ADP-ribose) polymerase (PARP) cleavage, release of cytochrome c (cyt c) into cytosol, and increase of Bax:Bcl-2 ratio. These results indicated that the induction of apoptosis by clitocine involved the multiple pathway including death receptor and mitochondrial pathways, and strongly suggested that the mitochondrial pathways were mediated by down-regulation of Bcl-2 and up-regulation of Bax, release of cytochrome c and subsequent activation of caspase-3 followed by down stream events leading to apoptotic mode of cell death.