Cancer chemoprevention using natural vitamin D and synthetic analogs

被引:87
作者
Guyton, KZ [1 ]
Kensler, TW
Posner, GH
机构
[1] CCS Associates, Mountain View, CA 94043 USA
[2] Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Arts & Sci, Dept Chem, Baltimore, MD 21218 USA
关键词
calcitriol analogs; 1; alpha; 25-dihydroxyvitamin D-3 analogs; deltanoids; hybrid deltanoids; noncalcemic deltanoids;
D O I
10.1146/annurev.pharmtox.41.1.421
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Substantial epidemiologic data support a role for vitamin D in cancer prevention. However, dose-limiting hypercalcemic effects have proved a major obstacle to the development of natural vitamin D as a cancer chemopreventive. Structure-activity studies have sought to disassociate the toxicities and chemopreventive activities of vitamin D, and a number of synthetic deltanoids (vitamin D analogs) have shown considerable promise in this regard. Several such compounds have chemopreventive efficacy in preclinical studies, as does natural vitamin D. Data supporting further development of agents of this class include in vitro and in vivo evidence of antiproliferative, proapoptotic, prodifferentiating and antiangiogenic activities. Ongoing studies are aimed at further defining the molecular mechanisms through which vitamin D and synthetic deltanoids affect gene expression and cellular fate. Additional efforts are focused on establishing the chemopreventive index (efficacy vs toxicity) of each synthetic deltanoid.
引用
收藏
页码:421 / 442
页数:22
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