title: 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.affiliation: General Surgery Department, Chang Gung Memorial Hospital, 222 Mai-Chin Road, Keelung 204, Taiwan ; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan.
authors.forename: Kun-Chun
authors.initials: KC
authors.lastname: Chiang
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Yeh
authors.forename: Shin-Cheh
authors.initials: SC
authors.lastname: Chen
authors.forename: Shih-Che
authors.initials: SC
authors.lastname: Shen
authors.forename: Jun-Te
authors.initials: JT
authors.lastname: Hsu
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
authors.forename: Jong-Hwei S
authors.initials: JH
authors.lastname: Pang
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Su
authors.forename: Masashi
authors.initials: M
authors.lastname: Takano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kittaka
authors.forename: Horng-Heng
authors.initials: HH
authors.lastname: Juang
authors.forename: Tai C
authors.initials: TC
authors.lastname: Chen