Influence of Berry Polyphenols on Receptor Signaling and Cell-Death Pathways: Implications for Breast Cancer Prevention

Abstract

Breast cancer is the most commonly diagnosed cancer among women worldwide. Many women have become more aware of the benefits of increasing fruit consumption, as part of a healthy lifestyle, for the prevention of cancer. The mechanisms by which fruits, including berries, prevent breast cancer can be partially explained by exploring their interactions with pathways known influence cell-proliferation and evasion of cell-death. Two receptor pathways- estrogen receptor (ER) and tyrosine kinase receptors, especially the epidermal growth factor receptor (EGFR) family- are drivers of cell-proliferation and play a significant role in the development of both primary and recurrent breast cancer. There is strong evidence to show that several phytochemicals present in berries such as cyanidin, delphinidin, quercetin, kaempferol, ellagic acid, resveratrol and pterostilbene, interact with and alter the effects of these pathways. Further, they also induce cell death (apoptosis and autophagy) via their influence on kinase signaling. In this review, we summarize in vitro data regarding the interaction of berry polyphenols with the specific receptors and the mechanisms by which they induce cell death. Further, we also present in vivo data of primary breast cancer prevention by individual compounds and whole berries. Finally, we present a possible role for berries and berry compounds in the prevention of breast cancer and our perspective on the areas that require further research.

Protective effects of berry polyphenols against age-related cognitive impairment

“…However, pterostilbene has been shown to display a higher in vivo bioavailability, possibly due to increased lipophilicity induced by the substitution of a methoxy rather than a hydroxyl group [176]. Pterostilbene is a molecule found in blueberries [177] and grapes [178]. Unfortunately, there are no reported estimates regarding pterostilbene intake in humans.…”

Estrogenic Potentials of Traditional Chinese Medicine

“…The Ganoderma lucidum (Reishi) extract inhibited the proliferation of both ERα-positive MCF-7 and ERα-negative MDA-MB-231cells, suggesting differential, albeit partially identical, regulations of cancer cell proliferation (Jiang et al, 2006). Pure chemicals, such as quercetin, kaempferol and resveratrol, collectively known as berry polyphenols, are supposed to demonstrate dose-dependent biphasic effects due to their competing effects against estrogen at high concentrations (Aiyer et al, 2012). Naringin, a flavanone glycoside isolated from Drynaria roosii (Gusuibu), was reported to act as estrogen at low concentrations and as anti-estrogen at high concentrations, presumably by selectively binding to ERβ .…”

Nutraceuticals: Curative Integrative Cancer Treatment

“…Anthocyanidins and anthocyanins: This group includes cyanidin, delphinidin, malvidin, peonidin, and petunidin, which are found in blueberries [43,46]. Carob fruit contains delphinidin, pelargonidin and cyanidin [47].…”