Journal
ARCHIVES OF TOXICOLOGY
Volume 86, Issue 2, Pages 263-273Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00204-011-0754-6
Keywords
Fisetin; Apoptosis; Cervical cancer; Caspase; ERK1/2; HeLa cell
Categories
Funding
- National Science Council, Taiwan [NSC 98-2314-B-040-024]
- Chung Shan Medical Hospital, Taichung, Taiwan [CSH-2011-C-026]
- National Science Council
- Ministry of Education
- Chung Shan Medical University
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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 40-6-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.
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