Phytoestrogens induce apoptosis through a mitochondria/caspase pathway in human breast cancer cells

Abstract

These data demonstrate that genistein, resveratrol, and quercetin have antiproliferative effects on breast cancer cells. Their induction of apoptosis involves the activation of both the intrinsic and extrinsic apoptotic pathways, which may be related to the differential affinity to ERα and ERβ. Whether phytoestrogens have similar effects on normal breast cells remains to be examined.

Impact of lower concentrations of phytoestrogens on the effects of estradiol in breast cancer cells

“…Our previous studies revealed that the distinctive expression of ER α and ER β may be associated with the apoptotic effects of these phytoestrogens (higher affinities for ER β) and the proliferative effect of E 2 in MCF-7 breast cancer cells (13,14). 8 necessary for proliferation and that ER β opposes the proliferative effects exerted by ER α (32)(33)(34).…”

“…We then observed both the zymogen and cleaved forms of caspases, including FADD, cytochrome C, tBid, caspase-9, and caspase-3. The decision to use a concentration of 10 −7 M to examine this signaling pathway was based on its effects on cell viability in the present study and in our previous reports (13) and also because of the range of plasma concentrations of phytoestrogens in humans (10nM-10μM) (15). The details of the experiment methods are described as follows.…”

“…These phytoestrogens have a lower binding affinity to ER α, but also exert partial anti-estrogenic effect due to their relative binding preference to ER β (11, 12). Our previous study demonstrated that the dichotomy of classic ER modulating action induced by phytoestrogens may result in different effects on mammalian tissue (13,14). However, in the presence of endogenous estrogen, the potential effects induced or modulated as a result of these phytoestrogens and their ER binding capabilities is a cause for concern.…”

Effect of Biochanin A versus 17β estradiol in rat submandibular salivary gland

“…These findings are consistent with those reported by Patisaul et al (49), wherein, ERβ was down-regulated by estrogen in a region specific manner in the rat brain, whereas exposure to coumestrol (phytoestrogen) is thought to modulate ERβ. Chen et al (50) observed the same contrasting pattern between E2 and a group of phytoestrogens (genistein, resveratrol, and quercetin) in the breast cancer cell line MCF-7.…”

Role of dietary bioactive natural products in estrogen receptor-positive breast cancer

“…The structure of quercetin is similar to estrogen, including two hydroxyl groups and a phenol ring [252]. Therefore, quercetin acts as a phytoestrogen that binds to the ER and participates in the regulation of cell growth and gene transcription through estrogen dependent pathway [253, 254] as well as via ER-independent pathway [157]. Quercetin has low bioavailability in humans [255].…”