19-Nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D 3 (MART-10) is a potent cell growth regulator with enhanced chemotherapeutic potency in liver cancer cells

Kun Chun Chiang, Chun Nan Yeh, Huang Yang Chen, Jim Ming Lee, Horng Heng Juang, Miin Fu Chen, Masashi Takano, Atsushi Kittaka, Tai C. Chen*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

41 引文 斯高帕斯(Scopus)

摘要

The discovery that the active form of vitamin D, 1α,25- dihydroxyvitamin D [1α,25(OH) 2D] can modulate cellular proliferation and differentiation of cancer cells has led to its potential application as a chemotherapeutic agent to treat a variety of cancers. However, the use of 1α,25(OH) 2D is limited due to its lethal side effect of hypercalcemia upon systemic administration. To overcome this drawback, numerous analogs have been synthesized. In this report, we examined the anti-proliferative activity of a new analog, 19-nor-2α-(3-hydroxypropyl)- 1α,25(OH) 2D 3 (MART-10), in HepG2 liver cancer cells, and studied the potential mechanisms mediating this action. We found that MART-10 exhibited approximately 100-fold greater activity than 1α,25(OH) 2D 3 in inhibiting HepG2 cell proliferation as determined by cell number counting method. MART-10 was also approximately 100-fold more potent than 1α,25(OH) 2D 3 in the upregulation of p21 and p27, that in turn arrested HepG2 cells at the G 0/G 1 phase to a greater extent. Given that no active caspase 3 was detected and treatment with 1α,25(OH) 2D 3 or MART-10 did not further increase the fractions of apoptotic and necrosis cells over the controls, the growth-inhibitory effect of 1α,25(OH) 2D 3 and MART-10 on HepG2 cells may not involve apoptosis. Overall, our findings suggest that MART-10 is a good candidate as a novel therapeutic regimen against liver cancer. Further pre-clinical studies using animal models and the subsequent human clinical trials are warranted.

原文英語
頁(從 - 到)1513-1519
頁數7
期刊Steroids
76
發行號13
DOIs
出版狀態已出版 - 11 12 2011

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