This study is to investigate the effect of
fascaplysin on human
cervical cancer cells (HeLa) in order to provide insights into the mechanisms of growth suppression involved in
fascaplysin-mediated apoptosis. Cytotoxic activity of
fascaplysin on HeLa cells was determined using MTT assay, cell cycle analysis, and apoptosis (
Annexin V-FITC and PI double staining) studies. The role of the molecules in cell cycle regulation and apoptosis was analyzed by Western blotting and flow cytometry.
Fascaplysin markedly inhibited HeLa cells proliferation in a dose-dependent manner, however, did not provoke G1 phase arrest in HeLa cells with downregulation of CDK4,
cyclin D1 and CDK4-specific Ser795 pRb phosphorylation. Furthermore,
fascaplysin induced significantly apoptosis evidenced by sub-G1 peak and
Annexin V-FITC and PI double staining. The molecular mechanism of
fascaplysin-induced apoptosis was characterized with the activation of
caspase-3, -8, and -9, truncation of Bid, release of
cytochrome c into cytosol, and down-regulation of Bcl-2 level.
Fascaplysin exhibits anti-proliferation effect towards human
cervical cancer HeLa cells through induction of apoptosis via extrinsic death pathway and mitochondrial pathway, but not arresting cell cycle progression at G1 phase. All together, these data sustain our contention that
fascaplysin has anticancer properties and merits further investigation as a potential therapeutic agent.