Inhibitors of the epidermal growth factor receptor in apple juice extract

Abstract

The polyphenol-rich extract of a consumer-relevant apple juice blend was found to potently inhibit the growth of the human colon cancer cell line HT29 in vitro. The epidermal growth factor receptor (EGFR) and its subsequent signaling cascade play an important role in the regulation of cell proliferation in HT29 cells. The protein tyrosine kinase activity of an EGFR preparation was effectively inhibited by the polyphenol-rich apple juice extract. Treatment of intact cells with this extract resulted in the suppression of the subsequent mitogen-activated protein kinase cascade. Amongst the so far identified apple juice constituents, the proanthocyanidins B1 and B2 as well as quercetin-3-glc (isoquercitrin) and quercetin-3-gal (hyperoside) were found to possess substantial EGFR-inhibitory properties. However, as to be expected from the final concentration of these potential EGFR inhibitors in the original polyphenol-rich extract, a synthetic mixture of the apple juice constituents identified and available so far, including both proanthocyanidins and the quercetin glycosides, showed only marginal inhibitory effects on the EGFR. These results permit the assumption that yet unknown constituents contribute substantially to the potent EGFR-inhibitory properties of polyphenol-rich apple juice extract. In summary, the polyphenol composition of apple juice possesses promising growth-inhibitory properties, affecting proliferation-associated signaling cascades in colon tumor cells.

Select Plant Tannins Induce IL-2Rα Up-Regulation and Augment Cell Division in γδ T Cells

“…The action of tannic acid is specific to CXCL12/ CXCR4 given that other chemokines/chemoattractants are not effected by this tannin preparation (70). Furthermore, apple tannins block Fc R1/IgE binding (55) and prevent epidermal growth factor signaling, presumably through physically blocking the receptor (57). Similar polyphenols from tea bind CD11b on monocytes, which we recently found for APP as well (43).…”

“…Interestingly, these illnesses are commonly associated with ␥␦ T cell regulatory activities (7,(51)(52)(53)(54), suggesting the described immunostimulatory properties of the Cat's Claw plant could be partially due to the activation of ␥␦ T cells. Preparations containing the apple-condensed tannins we described are also recognized for similar immunostimulatory properties (49,(55)(56)(57). These observations on the immunological effects of Cat's Claw and apple tannins support the prospect for condensed tannins to be used as a therapy to increase ␥␦ T cell function in innate immunity and wound healing.…”

Review of anticancer mechanisms of isoquercitin

“…They concluded that IQ is a promising antioxidant agent but that it did not inhibit Caco2 cellular growth [79] . In 2005, Kern et al [80] reported a perspective on the antiproliferative effect and demonstrated the potent EGFRinhibitory properties of polyphenolrich apple juice extract in adenocarcinoma colon in vitro model (HT29) [80] . Another study suggested that the beneficial effects of red wine on human health were attributable to the flavonoid content, which channeled the body metabolism towards Omethylation to yield compounds with potential protective effects against cancer [81] .…”

Resíduos de agrotóxicos em alimentos: uma preocupação ambiental global - Um enfoque às maçãs

“…[40][41][42] Esse aumento do consumo de maçãs pode ser atribuído, praticamente, a dois fatores: por ser um alimento de acesso fácil à população e, aos benefícios que esse alimento proporciona à saúde humana. [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] Entretanto, as pesquisas recentes revelam que as maçãs, principalmente as comercializadas e consumidas in natura, expõem as pessoas que as consomem, aumentando os riscos de contaminação por resíduos de agrotóxicos, podendo afetar diretamente a saúde. [58][59][60][61][62][63][64][65][66][67] Embora alguns resíduos de agrotóxicos encontrados nesses alimentos não excedam os limites máximos permitidos para o consumo humano, ainda não se conhecem exatamente os efeitos da acumulação, ao longo do tempo, desses compostos no organismo.…”