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Capsaicin-induced TRIB3 upregulation promotes apoptosis in cancer cells

Authors Lin RJ, Wu IJ, Hong JY, Liu BH, Liang RY, Yuan TM, Chuang SM

Received 12 January 2018

Accepted for publication 16 July 2018

Published 4 October 2018 Volume 2018:10 Pages 4237—4248

DOI https://doi.org/10.2147/CMAR.S162383

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 4

Editor who approved publication: Dr Kenan Onel


Rong-Jaan Lin,1,2 I-Jung Wu,1,2 Jo-Yu Hong,3 Bang-Hung Liu,4 Ruei-Yue Liang,4 Tein-Ming Yuan,5 Show-Mei Chuang4,6,7

1College of Life Sciences, National Chung Hsing University, 2Taichung Hospital, Ministry of Health and Welfare, 3Bachelor Program of Biotechnology, College of Agriculture and Natural Resources, 4Institute of Biomedical Sciences, College of Life Sciences, National Chung Hsing University, 5Surgery Department, Feng-Yuan Hospital, Ministry of Health and Welfare, 6Department of Nursing, Asia University, 7Department of Medical Research, China Medical University Hospital, Taichung, Taiwan

Background: Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is one of the main pungent components of chili peppers and has been shown to exert various effects on numerous physiological processes. Recent studies have focused on the chemopreventive effects of capsaicin, which can combat growth in various human cancer cell systems. The tribbles-related protein 3 (TRIB3) is evolutionarily conserved from Drosophila to humans. In the latter, TRIB3 is a key determinant in numerous cellular processes, including apoptosis.
Purpose: The aim of this study was to examine the importance of TRIB3 in the antitumor efficacy of capsaicin in human cancer cells, and further assess potential mechanism(s) underlying the capsaicin-induced upregulation of TRIB3.
Methods: Human cancer cell lines were treated with capsaicin, then evaluated for levels of TRIB3 and molecules related to apoptosis or signaling pathways. The impact of TRIB3 on capsaicin-induced apoptosis was investigated using si-RNA or overexpression of TRIB3.
Results: It is the first time to show that TRIB3 is targeted by capsaicin to promote apoptosis. Capsaicin promotes apoptotic cell death by upregulating TRIB3 expression in cancer cells. Overexpression of TRIB3 enhances capsaicin-induced apoptosis, and TRIB3 knockdown experiments demonstrate that the effect of capsaicin in apoptotic cell death is correlated with the induction of TRIB3 in cancer cells. Finally, enhancements in gene expression and protein stability are involved in the capsaicin-induced upregulation of TRIB3.
Conclusion: Our results show that the capsaicin-induced upregulation of TRIB3 triggers apoptosis and thereby contributes to the suppression of cell growth in cancer cell lines.

Keywords: capsaicin, TRIB3, apoptosis, cancer, Protein stability

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