MART-10, a New Generation of Vitamin D Analog, Is More Potent than 1 alpha, 25-Dihydroxyvitamin D-3 in Inhibiting Cell Proliferation and Inducing Apoptosis in ER+ MCF-7 Breast Cancer Cells

作者：Chiang Kun Chun; Yeh Chun Nan; Chen Shin Cheh; Shen Shih Che; Hsu Jun Te; Yeh Ta sen; Pang Jong Hwei S; Su Li Jen; Takano Masashi; Kittaka Atsushi; Juang Horng Heng^*; Chen Tai C

来源：Evidence-Based Complementary and Alternative Medicine, 2012, 310872.

DOI：10.1155/2012/310872

Hormone antagonist therapy for estrogen receptor positive (ER+) breast cancer patients post radical surgery and radiation therapy has a poor prognosis and also causes bone loss. 1 alpha, 25-dihydroxyvitamin D-3 [1 alpha, 25(OH)(2)D-3] is a potent antitumor agent in preclinical studies, but caused hypercalcemia when its effective antitumor doses were used. Therefore, we investigated the effects of a less-calcemic 1 alpha, 25(OH) 2D3 analog, 19-nor-2 alpha-(3-hydroxypropyl)-1 alpha, 25-dihydroxyvitamin D-3 (MART-10), on ER+ MCF-7 cells. We demonstrate that MART-10 is 500- to 1000-fold more potent than 1a, 25(OH)(2)D-3 in inhibiting cell growth in a dose-and time-dependent manner. MART-10 is also much more potent in arresting MCF-7cell cycle progression at G0/G1 phase as compared to 1 alpha, 25(OH)(2)D-3, possibly mediated by a greater induction of p21 and p27 expression. Moreover, MART-10 is more active than 1 alpha, 25(OH)(2)D-3 in causing cell apoptosis, likely through a higher BAX/Bcl expression ratio and the subsequent cytochrome C release from mitochondria to cytosol. Based on our in vitro findings, MART-10 could be a promising vitamin D analog for the potential treatment of breast cancer, for example, ER+ patients, to decrease the tumor relapse rate and the side effect on bone caused by antihormone regimens. Thus, further in vivo animal study is warranted.

• 出版日期2012
• 单位长春大学; 中央民族大学