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

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 D(3) [1α,25(OH)(2)D(3)] 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)(2)D(3) analog, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D(3 )(MART-10), on ER+MCF-7 cells. We demonstrate that MART-10 is 500- to 1000-fold more potent than 1α,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 G(0)/G(1) phase as compared to 1α,25(OH)(2)D(3), possibly mediated by a greater induction of p21 and p27 expression. Moreover, MART-10 is more active than 1α,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.

• Authors: Kun-Chun Chiang, Chun-Nan Yeh, Shin-Cheh Chen, Shih-Che Shen, Jun-Te Hsu, Ta-Sen Yeh, Jong-Hwei S Pang, Li-Jen Su, Masashi Takano, Atsushi Kittaka, Horng-Heng Juang, Tai C Chen
• Journal: Evidence-based complementary and alternative medicine : eCAM (Evid Based Complement Alternat Med) Vol. 2012 Pg. 310872 ( 2012) ISSN: 1741-4288 [Electronic] United States
• PMID: 23304196 (Publication Type: Journal Article)