Fisetin induces apoptosis in human cervical cancer HeLa cells through ERK1/2-mediated activation of caspase-8-/caspase-3-dependent pathway.

Abstract

Fisetin is a naturally occurring flavonoid that has been reported to inhibit the proliferation and to induce apoptotic cell death in several tumor cells. However, the apoptosis-inducing effect of fisetin on tumor cell lines was investigated besides HeLa cells. In this study, we found that fisetin induced apoptosis of HeLa cells in a dose- and time-dependent manner, as evidenced by nuclear staining of 4'-6-Diamidino-2-phenylindole (DAPI), flow cytometry assay, and Annexin-V/PI double-labeling. In addition, fisetin triggered the activations of caspases-3 and -8 and the cleavages of poly (ADP-ribose) polymerase, resulting in apoptosis induction. Moreover, treatment of HeLa cells with fisetin induced a sustained activation of the phosphorylation of ERK1/2, and inhibition of ERK1/2 by PD98059 (MEK1/2 inhibitor) or transfection with the mutant ERK1/2 expression vector significantly abolished the fisetin-induced apoptosis through the activation of caspase-8/-3 pathway. The in vivo xenograft mice experiments revealed that fisetin significantly reduced tumor growth in mice with HeLa tumor xenografts. In conclusion, our results indicated that fisetin exhibited anti-cancer effect and induced apoptosis in HeLa cell lines both in vitro and in vivo.

• Authors: Tsung-Ho Ying, Shun-Fa Yang, Su-Ju Tsai, Shu-Ching Hsieh, Yi-Chang Huang, Da-Tian Bau, Yi-Hsien Hsieh
• Journal: Archives of toxicology (Arch Toxicol) Vol. 86 Issue 2 Pg. 263-73 (Feb 2012) ISSN: 1432-0738 [Electronic] Germany
• PMID: 21964635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Flavonoids
• Flavonols
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Caspase 3
• Caspase 8
• fisetin

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Enzyme Activation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Flavonoids (pharmacology)
• Flavonols
• HeLa Cells
• Humans
• Mice
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Uterine Cervical Neoplasms (drug therapy, metabolism, pathology)