Safrole Induces Apoptosis in Human Oral Cancer HSC-3 Cells

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 per...

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Bibliographic Details
Published in:Journal of dental research 2011-02, Vol.90 (2), p.168-174
Main Authors: Yu, F.-S., Yang, J.-S., Yu, C.-S., Lu, C.-C., Chiang, J.-H., Lin, C.-W., Chung, J.-G.
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Antineoplastic agents
Apoptosis
Biological and medical sciences
Calcium - metabolism
Carcinoma, Squamous Cell - drug therapy
Caspase 3 - metabolism
Caspase 8 - metabolism
Caspase 9 - metabolism
Cell Line, Tumor - drug effects
Chemotherapy
Cytochromes c - metabolism
DNA Damage
Fas Ligand Protein - metabolism
Humans
Male
Medical sciences
Membrane Potential, Mitochondrial - drug effects
Mice
Mice, Nude
Mouth Neoplasms - drug therapy
Neoplasm Transplantation
Otorhinolaryngology. Stomatology
Pharmacology. Drug treatments
Safrole - pharmacology
Safrole - therapeutic use
Statistics, Nonparametric
Tumors
Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
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Summary: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 Ca2+ 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 Ca2+ and by mitochondria- and Fas-dependent pathways.
ISSN:0022-0345
1544-0591
DOI:10.1177/0022034510384619