Safrole induces apoptosis in human oral cancer HSC-3 cells.

Abstract

Phytochemicals have been used as potential chemopreventive or chemotherapeutic agents. However, there are data suggesting a mutagenic effect of some phytochemicals. We hypothesized that safrole would have anticancer effects on human oral squamous cell carcinoma HSC-3 cells. Safrole decreased the percentage of viable HSC-3 cells via induction of apoptosis by an increased level of cytosolic Ca(2+) and a reduction in the mitochondrial membrane potential (ΔΨ(m)). Changes in the membrane potential were associated with changes in the Bax, release of cytochrome c from mitochondria, and activation of downstream caspases-9 and -3, resulting in apoptotic cell death. In vivo studies also showed that safrole reduced the size and volume of an HSC-3 solid tumor on a xenograft athymic nu/nu mouse model. Western blotting and flow cytometric analysis studies confirmed that safrole-mediated apoptotic cell death of HSC-3 cells is regulated by cytosolic Ca(2+) and by mitochondria- and Fas-dependent pathways.

• Authors: F-S Yu, J-S Yang, C-S Yu, C-C Lu, J-H Chiang, C-W Lin, J-G Chung
• Journal: Journal of dental research (J Dent Res) Vol. 90 Issue 2 Pg. 168-74 (Feb 2011) ISSN: 1544-0591 [Electronic] United States
• PMID: 21173435 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fas Ligand Protein
• Cytochromes c
• Caspase 3
• Caspase 8
• Caspase 9
• Safrole
• Calcium

Topics

• Analysis of Variance
• Animals
• Apoptosis
• Calcium (metabolism)
• Carcinoma, Squamous Cell (drug therapy)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Caspase 9 (metabolism)
• Cell Line, Tumor (drug effects)
• Cytochromes c (metabolism)
• DNA Damage
• Fas Ligand Protein (metabolism)
• Humans
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Mice, Nude
• Mouth Neoplasms (drug therapy)
• Neoplasm Transplantation
• Safrole (pharmacology, therapeutic use)
• Statistics, Nonparametric