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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.

Abstract
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.
AuthorsFu-Shun Yu, An-Cheng Huang, Jai-Sing Yang, Chun-Shu Yu, Chi-Cheng Lu, Jo-Hua Chiang, Chang-Fang Chiu, Jing-Gung Chung
JournalEnvironmental toxicology (Environ Toxicol) Vol. 27 Issue 7 Pg. 433-44 (Jul 2012) ISSN: 1522-7278 [Electronic] United States
PMID21591240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Wiley Periodicals, Inc.
Chemical References
  • bcl-2-Associated X Protein
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Safrole
Topics
  • Apoptosis (drug effects)
  • Carcinoma, Squamous Cell (pathology)
  • Caspase 3 (metabolism)
  • Caspase 8 (metabolism)
  • Caspase 9 (metabolism)
  • Cell Line, Tumor
  • Cell Survival
  • DNA Damage (drug effects)
  • Humans
  • Mitochondria (drug effects)
  • Safrole (pharmacology)
  • Signal Transduction (drug effects)
  • Tongue Neoplasms (pathology)
  • bcl-2-Associated X Protein (metabolism, pharmacology)

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