[Anti-proliferation of human cervical cancer HeLa cell line by fascaplysin through apoptosis induction].
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.
Lu
Xiao-Ling
XL
Ningbo University, Key Laboratory of Applied Marine Biotechnology, Ministry ofEducation, Ningbo 315211, China.
Zheng
Yan-Ling
YL
Chen
Hai-Min
HM
Yan
Xiao-Jun
XJ
Wang
Feng
F
Xu
Wei-Feng
WF
D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D000644:Quaternary Ammonium Compounds; D002243:Carbolines; D007212:Indolizines
D007211:Indoles; C069346:fascaplysine; D000644:Quaternary Ammonium Compounds; D002243:Carbolines; D007212:Indolizines