Efficacy and Mechanism of Action of 1α-hydroxy-24-ethyl-Cholecalciferol (1α[OH]D5) in Breast Cancer Prevention and Therapy
It is now well established that the active metabolite of vitamin D3, 1α,25(OH)2D3, regulates cell growth and differentiation in various in vitrocancer models. However, its clinical use is precluded due to its hypercalcemicactivity in vivo. Hence, several less calcemic vitamin D analogs have been synthesizedand evaluated for their chemopreventive and therapeutic efficacy inexperimental carcinogenesis models. A novel analog of vitamin D3, 1α-hydroxy-24-ethyl-cholecalciferol (1α[OH]D5), has currently been under investigationin our laboratory for its application in breast cancer prevention andtherapy. 1α(OH)D5 had been shown to inhibit development of estrogen-andprogesterone-dependent ductal lesions as well as steroid hormone-independentalveolar lesions in a mammary gland organ culture (MMOC) model. Moreover, the inhibitory effect was more significant if 1α(OH)D5 was presentduring the promotional phase of the lesion development. The growth inhibitoryeffect of 1α(OH)D5 has also been manifested in several breast cancer celllines, including BT-474 and MCF-7. Breast cancer cell lines that responded to1a(OH)D5 treatment were vitamin D receptor positive (VDR+). Vitamin D receptor-negative (VDR_) cell lines, such as MDA-MB-231 and MDA-MB-435, did not show growth inhibition upon incubation with 1α(OH)D5.
KeywordsToxicity Estrogen Osteoporosis Oncol Tamoxifen
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