Induction of apoptosis by casticin in cervical cancer cells through reactive oxygen species-mediated mitochondrial signaling pathways.

Abstract

Casticin, one of the main components from Fructus Viticis, has been reported to inhibit the growth of various cancer cells, including the human cervical cancer cell line HeLa. The purpose of this study was to examine the apoptotic activity and molecular mechanism of casticin action on human cervical cancer cells. The apoptotic activity of casticin on human cervical cancer HeLa, CasKi, SiHa and peripheral blood mononuclear cells (PBMCs) was measured using a histone/DNA ELISA assay, flow cytometry with propidium iodide (PI) staining and DNA agarose gel electrophoresis. The mitochondrial membrane potential and reactive oxygen species (ROS) production were evaluated by flow cytometry analysis. Caspase activities were assayed using a caspase colorimetric activity assay kit. Protein expression levels of cytochrome c, Bax, Bcl-2, Bcl-xL and XIAP were analyzed by Western blotting. Casticin caused accumulation of the Sub-G1 cells and increased reactive oxygen species (ROS) production in HeLa, CasKi, SiHa cell lines, but not in PBMCs. Apoptosis of HeLa cells was induced by casticin via mitochondrial release of cytochrome c due to the reduction of mitochondrial trans-membrane potential, activation of caspase-3 and -9, and the production of reactive oxygen species. The pan caspase inhibitor zVAD-FMK, the caspase-9 inhibitor zLEHD-fmk and N-acetylcysteine suppressed casticin-induced apoptosis. Bax was upregulated, while expression levels of Bcl-xL and XIAP were downregulated. However, there was no change in the expression of Bcl-2 under the same treatment. Our results indicate that casticin-induced apoptosis of cervical cancer cells is mediated by ROS generation and mitochondrial signaling pathways.

• Authors: Dan Chen, Jianguo Cao, Li Tian, Fei Liu, Xifeng Sheng
• Journal: Oncology reports (Oncol Rep) Vol. 26 Issue 5 Pg. 1287-94 (Nov 2011) ISSN: 1791-2431 [Electronic] Greece
• PMID: 21725610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Flavonoids
• Reactive Oxygen Species
• casticin
• Caspases

Topics

• Apoptosis (drug effects)
• Caspases (metabolism)
• Female
• Flavonoids (pharmacology)
• HeLa Cells
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Uterine Cervical Neoplasms (drug therapy, metabolism, pathology)