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.
Highlights
Chili pepper is a widely consumed spice in various countries with multiple studies reporting its impact on health
To examine the chemopreventive potential of chili pepper components (Figure 1A), we investigated their inhibitory activities against neoplastic cell transformation induced by epidermal growth factor (EGF) stimulation
Anchorage-independent growth in agar was examined after chili pepper compounds and EGF were treated to JB6 P+ cells
Summary
Chili pepper (fruits from the plants of Capsicum) is a widely consumed spice in various countries with multiple studies reporting its impact on health. Chili pepper components can be divided into capsaicinoids, capsinoids, and carotenoids. The most abundant capsaicinoids in chili peppers are capsaicin (N-[(4-hydroxy-3-methoxypheny) methyl]-8-methyl-E-6-nonenamide) and dihydrocapsaicin (N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methyl-6-nonanamide) [1]. Capsinoids include capsiate, dihydrocapsiate, and nordihydrocapsiate [2]. Carotenoids are major sources responsible for the red color in chili peppers, with capsanthin contributing the highest portion in most of the varieties [3]. Chili pepper and its constituents are reported to exert pain relief, anti-inflammatory, anti-oxidative, anti-obesity, and anti-cancer effects [2,4,5]. Studies on the cancer preventive/therapeutic effects of chili
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