【摘 要】
：
Phytonutrients such as carotenoids, polyphenols and isothiocyanates were found by us to inhibit sex steroid signaling, the major risk factor for breast cancer.However, estrogens are beneficial for bon
【机 构】
：
Department of Clinical Biochemistry Faculty of Health Sciences and Soroka Medical Center Ben Gurion
【出 处】
：
BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会)
论文部分内容阅读
Phytonutrients such as carotenoids, polyphenols and isothiocyanates were found by us to inhibit sex steroid signaling, the major risk factor for breast cancer.However, estrogens are beneficial for bone health.Thus, the aim of the study was to determine whether phytonutrients, which inhibit estrogen signaling in cancer cells, do not inhibit its positive action in bone cells.The phytonutrients which inhibit estrogen activity in T47D breast cancer cells do not inhibit such activity in two bone cell lines, MC3T3-E1 mouse calvaria osteoblast like cells and MG-63 human osteosarcoma cells stably transfected with estrogen receptor alpha (ERα).Moreover, some of them stimulated estrogen induced reporter gene activity and enhanced transcription and activity of the bone forming genes, alkaline phosphatase, osteocalcin and osteoprotegerin.These effects of phytonutrients on estrogenic activity were associated with increased nuclear (ERα) levels in the bone cells but not in the breast cancer cells.In addition, the phytonutrients transactivated the antioxidant response element transcription system in both, the bone and the breast cancer cells.Thus, we studied the role of Nrf2, the major transcription factor of this system, in the differential effects on phytonutrients on estrogenic activity.Overexpression of Nrf2 inhibited estrogen induced transcription in breast cancer cells but enhanced it in bone cells and reduction of Nrf2 level using siRNA leads to a decrease in phytonutrient-induced estrogen reporter gene activity in the bone cells.In conclusion, Phytonutrients, which inhibit estrogenic activity in cancer cells, do not inhibit and even stimulate it in bone cells.
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