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- Title
MART-10, a New Generation of Vitamin D Analog, Is More Potent than 1α,25-Dihydroxyvitamin D<sub>3</sub> in Inhibiting Cell Proliferation and Inducing Apoptosis in ER+ MCF-7 Breast Cancer Cells.
- 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
- 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 preclinical 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 alsomuchmore 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.
- Publication
Evidence-based Complementary & Alternative Medicine (eCAM), 2012, Vol 2012, p1
- ISSN
1741-427X
- Publication type
Article
- DOI
10.1155/2012/310872