The phytoestrogens daidzein and equol inhibit the drug transporter BCRP/ABCG2 in breast cancer cells: potential chemosensitizing effect

Abstract

In contrast to previous reports for genistein, daidzein and equol do not provoke a major up-regulation of the transporter expression but instead an inhibition of BCRP activity and sensitization to BCRP substrates.

Equol: A Microbiota Metabolite Able to Alleviate the Negative Effects of Zearalenone during In Vitro Culture of Ovine Preantral Follicles

“…This can be explained by the short-term in vitro culture for these types of cells [58], as well as the tested concentrations of the substances. For instance, ABCG2 is usually upregulated by ZEN [27] and downregulated by equol [26], but no differences were observed in the present study.…”

“…Importantly, although both ZEN and equol are xenoestrogens and are usually originated from the same feedstuffs, they act differently. For instance, (i) equol preferentially binds oestrogen receptor (ER)-β, while ZEN has more affinity to ER-α; (ii) equol is a co-substrate to prostaglandin H synthase (PHS)-peroxidase stimulating PHS cyclooxygenase, while ZEN is an inhibitor [25]; (iii) equol inhibits the expression of the multidrug resistance protein ATP-binding cassette, subfamily G, member 2 (ABCG2 or BCRP [breast cancer resistance protein]) [26], while ZEN is an ABCG2 substrate [27]; and (iv) equol is not an antioxidant itself, but triggers cell signalling pathways to induce the synthesis of antioxidant enzymes [17], while ZEN induces oxidative stress [28]. Although these compounds are not often competing for the same oestrogen receptors, we hypothesise that the antioxidant and anti-inflammatory effects of equol may minimise the toxic effect of ZEN.…”

Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy

“…Rigalli et al studied in vitro the effects of daidzein use in breast cancer therapy [ 139 ]. In one of those studies, they proved that daidzein downregulated the expression of multidrug resistance-associated protein 1 (MRP1) in both Michigan Cancer Foundation-7 (MCF-7) and MDA-MB-231 breast cancer cell lines.…”

Alleviation of Multidrug Resistance by Flavonoid and Non-Flavonoid Compounds in Breast, Lung, Colorectal and Prostate Cancer

“…According to Li and co-workers (2005), genistein pre-treatment of prostate and lung cancer cells inhibits NF-κB activity and contributes to increased growth inhibition and apoptosis induced by cisplatin and docetaxel [207]. Another isoflavone, daidzein, found in soybeans, inhibited BCRP and MRP1/2 drug transporters, therefore sensitizing breast cancer cells to chemotherapeutic agents (mitoxantrone, doxorubicin) [208].…”