MART-10, a new generation of vitamin d analog, is more potent than 1 α,25-dihydroxyvitamin Din inhibiting cell proliferation and inducing apoptosis in ER+ MCF-7 breast cancer cells

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

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

Original languageEnglish
Article number310872
JournalEvidence-based Complementary and Alternative Medicine
Volume2012
DOIs
StatePublished - 2012

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