title: 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.affiliation: Department of Dental Hygiene, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: F-S
authors.initials: FS
authors.lastname: Yu
authors.forename: J-S
authors.initials: JS
authors.lastname: Yang
authors.forename: C-S
authors.initials: CS
authors.lastname: Yu
authors.forename: C-C
authors.initials: CC
authors.lastname: Lu
authors.forename: J-H
authors.initials: JH
authors.lastname: Chiang
authors.forename: C-W
authors.initials: CW
authors.lastname: Lin
authors.forename: J-G
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D012451:Safrole / Q000494:pharmacology* / Q000627:therapeutic use; D018709:Statistics, Nonparametric
chemical_list: D053222:Fas Ligand Protein; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D012451:Safrole; D002118:Calcium