title: Polyphenols, isothiocyanates, and carotenoid derivatives enhance estrogenic activity in bone cells but inhibit it in breast cancer cells.
abstract: While exposure to estrogens is a major risk factor of breast and endometrial cancer, it well established that estrogens are beneficial for bone health. We have previously shown that carotenoids inhibit estrogen signaling in breast and endometrial cancer cells. The aim of this study was to compare the effects of various phytonutrients, (carotenoid derivatives, polyphenols, isothiocyanates) on estrogenic activity in breast cancer cells and osteoblast-like cells. All the tested phytonutrients inhibited estrogen response element (ERE) transactivation in breast cancer cells. In contrast, these compounds either did not affect or enhanced ERE activity and the expression of several bone-forming genes. These results were obtained using two osteoblast-like cell lines, MG-63 human osteosarcoma cells stably transfected with estrogen receptor-α (ERα) and MC3T3-E1 mouse calvaria-derived cells expressing endogenous ER. Phytonutrients-induced ERE inhibition in breast cancer cells, and its potentiation in osteoblast-like cells were associated both with a decrease and a rise in total and nuclear ERα levels, respectively. Phytonutrients activated the electrophile/antioxidant response element (EpRE/ARE) transcription system to various extents in both cancer and bone cell lines. Overexpression of Nrf2, the major EpRE/ARE activating transcription factor, mimicked the effects of phytonutrients, causing inhibition and enhancement of ERE transactivation in breast cancer cells and in osteoblast-like cells, respectively. Moreover, reduction in Nrf2 levels by RNAi led to a decrease in the phytonutrient potentiation of ERE activity transactivation in osteoblast-like cells. These findings suggest that the enhancement and inhibition of estrogen signaling by phytonutrients in bone-derived cells and breast cancer cells, respectively, is partially mediated by the activation of the Nrf2/ARE system.
authors: Dept. of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion Univ. of the Negev, PO Box 653, Beer Sheva, Israel.
authors: Anna
authors: A
authors: Veprik
authors: Marina
authors: M
authors: Khanin
authors: Karin
authors: K
authors: Linnewiel-Hermoni
authors: Michael
authors: M
authors: Danilenko
authors: Joseph
authors: J
authors: Levy
authors: Yoav
authors: Y
authors: Sharoni
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism*; D002338:Carotenoids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000032:analysis; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D059808:Polyphenols / Q000494:pharmacology*; D034622:RNA Interference; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D059808:Polyphenols; D002338:Carotenoids