Vitamin A Enhances Antitumor Effect of a Green Tea Polyphenol on Melanoma by Upregulating the Polyphenol Sensing Molecule 67-kDa Laminin Receptor

Abstract

BackgroundGreen tea consumption has been shown to have cancer preventive qualities. Among the constituents of green tea, (-)-Epigallocatechin-3-O-gallate (EGCG) is the most effective at inhibiting carcinogenesis. However, the concentrations of EGCG that are required to elicit the anticancer effects in a variety of cancer cell types are much higher than the peak plasma concentration that occurs after drinking an equivalent of 2–3 cups of green tea. To obtain the anticancer effects of EGCG when consumed at a reasonable concentration in daily life, we investigated the combination effect of EGCG and food ingredient that may enhance the anticancer activity of EGCG on subcutaneous tumor growth in C57BL/6N mice challenged with B16 melanoma cells.Methodology/Principal FindingsAll-trans-retinoic acid (ATRA) enhanced the expression of the 67-kDa laminin receptor (67LR) and increased EGCG-induced cell growth inhibition in B16 melanoma cells. The cell growth inhibition seen with the combined EGCG and ATRA treatment was abolished by treatment with an anti-67LR antibody. In addition, the combined EGCG and ATRA treatment significantly suppressed the melanoma tumor growth in mice. Expression of 67LR in the tumor increased upon oral administration of ATRA or a combined treatment of EGCG and ATRA treatment. Furthermore, RNAi-mediated silencing of the retinoic acid receptor (RAR) α attenuated the ATRA-induced enhancement of 67LR expression in the melanoma cells. An RAR agonist enhanced the expression levels of 67LR and increased EGCG-induced cell growth inhibition.Conclusions/SignificanceOur findings provide a molecular basis for the combination effect seen with dietary components, and indicate that ATRA may be a beneficial food component for cancer prevention when combined with EGCG.

Improving anticancer efficacy of (-)-epigallocatechin-3-gallate gold nanoparticles in murine B16F10 melanoma cells

“…So far as we know, this is the first case using physically derived gold nanoparticles in conjunction with EGCG with ultrasound preprocessing against melanoma. Combined treatment with EGCG and vorinostat or vitamin A has also shown improved and enhanced anti-melanoma efficacy 30,31. In our previous study, EGCG-pNG was also proven to access synergistic anti-cancer ability against bladder cancer 15,22…”

Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion

“…Given the aggressive nature of melanomas, effective therapies may most likely involve a combinational approach. In fact, EGCG has been shown to have a stronger anti-melanoma effect when used in conjunction with vitamin A [27], vorinostat [28], interferon [29], DNA vaccination [30], dacarbazine [31], and even red light [32]. This combinational treatment will likely decrease the doses required for either medication, and consequently decrease the adverse effects associated with these therapies.…”

Green tea polyphenols and their potential role in health and disease

“…DOX encapsulated in 6-O-(3-hexadecyloxy-2-hydroxypropyl)-hyaluronic acid nanoparticles, 9HDHA-NPs, with EGCG significantly inhibits the growth of Ehrlich ascites tumors (Ray et al 2013). Further, EGCG in combination with vitamin A or ascorbic acid has been reported to show beneficial effects for B16 melanoma and other types of cancer prevention (Gao et al 2013;Lee et al 2010;Wel et al 2003). …”