Capsaicin induces apoptosis in SCC-4 human tongue cancer cells through mitochondria-dependent and -independent pathways.

Abstract

Although there have been advances in the fields of surgery, radiotherapy, and chemotherapy of tongue cancer, the cure rates are still not substantially satisfactory. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the major pungent ingredient of hot chili pepper and has been reported to have an antitumor effect on many human cancer cell types. The molecular mechanisms of the antitumor effect of capsaicin are not yet completely understood. Herein, we investigated whether capsaicin induces apoptosis in human tongue cancer cells. Capsaicin decreased the percentage of viable cells in a dose-dependent manner in human tongue cancer SCC-4 cells. In addition, capsaicin produced DNA fragmentation, decreased the DNA contents (sub-G1 phase), and induced G0/G1 phase arrest in SCC-4 cells. We demonstrated that capsaicin-induced apoptosis is associated with an increase in reactive oxygen species and Ca²⁺ generations and a disruption of the mitochondrial transmenbrane potential (ΔΨ(m)). Treatment with capsaicin induced a dramatic increase in caspase-3 and -9 activities, as assessed by flow cytometric methods. A possible mechanism of capsaicin-induced apoptosis is involved in the activation of caspase-3 (one of the apoptosis-executing enzyme). Confocal laser microscope examination also showed that capsaicin induced the releases of AIF, ATF-4, and GADD153 from mitochondria of SCC-4 cells.

• Authors: Siu-Wan Ip, Sheng-Hui Lan, An-Cheng Huang, Jai-Sing Yang, Ya-Yin Chen, Hui-Ying Huang, Zen-Pin Lin, Yuan-Man Hsu, Mei-Due Yang, Chang-Fang Chiu, Jing-Gung Chung
• Journal: Environmental toxicology (Environ Toxicol) Vol. 27 Issue 6 Pg. 332-41 (May 2012) ISSN: 1522-7278 [Electronic] United States
• PMID: 20925121 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Wiley Periodicals, Inc.

Chemical References

• Reactive Oxygen Species
• Caspase 3
• Capsaicin
• Calcium

Topics

• Apoptosis (drug effects)
• Calcium (metabolism)
• Capsaicin (pharmacology, therapeutic use)
• Caspase 3 (metabolism)
• Cell Cycle
• Cell Line, Tumor
• DNA Fragmentation (drug effects)
• Endoplasmic Reticulum Stress
• Humans
• Mitochondria (metabolism)
• Reactive Oxygen Species (metabolism)
• Tongue Neoplasms (drug therapy)
• Tumor Cells, Cultured