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Safrole induces cell death in human tongue squamous cancer SCC‐4 cells through mitochondria‐dependent caspase activation cascade apoptotic signaling pathways
Author(s) -
Yu FuShun,
Huang AnCheng,
Yang JaiSing,
Yu ChunShu,
Lu ChiCheng,
Chiang JoHua,
Chiu ChangFang,
Chung JingGung
Publication year - 2012
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.20658
Subject(s) - safrole , apoptosis , fadd , dapi , chemistry , caspase , cancer research , squamous carcinoma , microbiology and biotechnology , caspase 8 , signal transduction , cancer cell , cytochrome c , biology , programmed cell death , biochemistry , cancer , carcinoma , genetics , chromatography
Safrole is one of important food‐borne phytotoxin that exhibits in many natural products such as oil of sassafras and spices such as anise, basil, nutmeg, and pepper. This study was performed to elucidate safrole‐induced apoptosis in human tongue squamous carcinoma SCC‐4 cells. The effect of safrole on apoptosis was measured by flow cytometry and DAPI staining and its regulatory molecules were studied by Western blotting analysis. Safrole‐induced apoptosis was accompanied with up‐regulation of the protein expression of Bax and Bid and down‐regulation of the protein levels of Bcl‐2 (up‐regulation of the ratio of Bax/Bcl‐2), resulting in cytochrome c release, promoted Apaf‐1 level and sequential activation of caspase‐9 and caspase‐3 in a time‐dependent manner. We also used real‐time PCR to show safrole promoted the mRNA expressions of caspase‐3, ‐8, and ‐9 in SCC‐4 cells. These findings indicate that safrole has a cytotoxic effect in human tongue squamous carcinoma SCC‐4 cells by inducing apoptosis. The induction of apoptosis of SCC‐4 cells by safrole is involved in mitochondria‐ and caspase‐dependent signal pathways. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2012.