Dihydrocapsaicin Inhibits Epithelial Cell Transformation through Targeting Amino Acid Signaling and c-Fos Expression.

Abstract

Chili peppers are one of the most widely consumed spices worldwide. However, research on the health benefits of chili peppers and some of its constituents has raised controversy as to whether chili pepper compounds possess cancer-promoting or cancer-preventive effects. While ample studies have been carried out to examine the effect of capsaicin in carcinogenesis, the chemopreventive effect of other major components in chili pepper, including dihydrocapsaicin, capsiate, and capsanthin, is relatively unclear. Herein, we investigated the inhibitory effect of chili pepper components on malignant cell transformation. Among the tested chili pepper compounds, dihydrocapsaicin displayed the strongest inhibitory activity against epidermal growth factor (EGF)-induced neoplastic transformation. Dihydrocapsaicin specifically suppressed EGF-induced phosphorylations of the p70S6K1-S6 pathway and the expression of c-Fos. A reduction in c-Fos levels by dihydrocapsaicin led to a concomitant downregulation of AP-1 activation. Further analysis of the molecular mechanism responsible for the dihydrocapsaicin-mediated decrease in phospho-p70S6K1, revealed that dihydrocapsaicin can block amino acid-dependent mechanistic targets of rapamycin complex 1 (mTORC1)-p70S6K1-S6 signal activation. Additionally, dihydrocapsaicin was able to selectively augment amino acid deprivation-induced cell death in mTORC1-hyperactive cells. Collectively, dihydrocapsaicin exerted chemopreventive effects through inhibiting amino acid signaling and c-Fos pathways and, thus, might be a promising cancer preventive natural agent.

• Authors: Ji Su Lee, Yeong A Kim, Young Jin Jang, Yongtaek Oh, Sanguine Byun
• Journal: Nutrients (Nutrients) Vol. 11 Issue 6 (Jun 04 2019) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 31167465 (Publication Type: Journal Article)

Chemical References

• Amino Acids
• Epidermal Growth Factor
• Cyclooxygenase 2
• Ribosomal Protein S6 Kinases, 70-kDa
• ribosomal protein S6 kinase, 70kD, polypeptide 1
• Tetradecanoylphorbol Acetate
• Capsaicin
• dihydrocapsaicin

Topics

• Amino Acids (metabolism)
• Animals
• Capsaicin (analogs & derivatives, chemistry, pharmacology)
• Cell Line
• Cell Survival (drug effects)
• Cyclooxygenase 2 (genetics, metabolism)
• Epidermal Growth Factor (genetics, metabolism)
• Epithelial Cells (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Fibroblasts (drug effects)
• Gene Expression Regulation (drug effects)
• Genes, fos (genetics, physiology)
• Humans
• Mice
• Molecular Structure
• Phosphorylation
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• Tetradecanoylphorbol Acetate (metabolism)