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Evidence-Based Complementary and Alternative Medicine
Volume 2012 (2012), Article ID 310872, 10 pages
http://dx.doi.org/10.1155/2012/310872
Research Article

MART-10, a New Generation of Vitamin D Analog, Is More Potent than 1α,25-Dihydroxyvitamin D3 in Inhibiting Cell Proliferation and Inducing Apoptosis in ER+ MCF-7 Breast Cancer Cells

1General Surgery Department, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung 204, Taiwan
2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan
3General Surgery Department, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan 333, Taiwan
4Institute of Systems Biology and Bioinformatics, National Central University, Jhongli City, Taoyuan 32001, Taiwan
5Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan
6Department of Anatomy, College of Medicine, Chang Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Taoyuan 333, Taiwan
7Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA

Received 28 September 2012; Accepted 21 November 2012

Academic Editor: Martin Kohlmeier

Copyright © 2012 Kun-Chun Chiang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is a potent antitumor agent in pre-clinical studies, but caused hypercalcemia when its effective antitumor doses were used. Therefore, we investigated the effects of a less-calcemic 1α,25(OH)2D3 analog, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), on ER+MCF-7 cells. We demonstrate that MART-10 is 500- to 1000-fold more potent than 1α,25(OH)2D3 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 1α,25(OH)2D3, possibly mediated by a greater induction of p21 and p27 expression. Moreover, MART-10 is more active than 1α,25(OH)2D3 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.