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Title: Inecalcitol, an analog of 1α,25(OH) 2D 3, induces growth arrest of androgen-dependent prostate cancer cells
Authors: Okamoto, R.
Delansorne, R.
Wakimoto, N.
Doan, N.B.
Akagi, T.
Shen, M.
Ho, Q.H.
Said, J.W.
Koeffler, H.P. 
Keywords: antiproliferative effects
prostate cancer
vitamin D
Issue Date: 15-May-2012
Citation: Okamoto, R., Delansorne, R., Wakimoto, N., Doan, N.B., Akagi, T., Shen, M., Ho, Q.H., Said, J.W., Koeffler, H.P. (2012-05-15). Inecalcitol, an analog of 1α,25(OH) 2D 3, induces growth arrest of androgen-dependent prostate cancer cells. International Journal of Cancer 130 (10) : 2464-2473. ScholarBank@NUS Repository.
Abstract: 19-nor-14-epi-23-yne-1,25(OH) 2D 3 (inecalcitol) is a unique vitamin D 3 analog. We evaluated the activity of inecalcitol in a human prostate cancer model system. The analog was 11-fold more potent than 1,25(OH) 2D 3 in causing 50% clonal growth inhibition of androgen-sensitive human prostate cancer LNCaP cells. Inecalcitol, more than 1,25(OH) 2D 3, reduced in a dose-dependent manner the expression levels of the transcription factor ETS variant 1 and the serine/threonine protein kinase Pim-1, both of which are upregulated in prostate cancer. Remarkably, dose challenge experiments revealed that inecalcitol maximal tolerated dose (MTD) by intraperitoneal (i.p.) administration was 30 μg/mouse (1,300 μg/kg) three times per week, while we previously found that the MTD of 1,25(OH) 2D 3 is 0.0625 μg/mouse; therefore, inecalcitol is 480 times less hypercalcemic than 1,25(OH) 2D 3. Pharmacokinetic studies showed that plasma half-life of inecalcitol were 18.3 min in mice. A xenograft model of LNCaP cells was developed in immunodeficient mice treated with inecalcitol. The tumors of the diluent-treated control mice increased in size but those in the inecalcitol treatment group did not grow. Our data suggest that inecalcitol inhibits androgen-responsive prostate cancer growth in vivo and should be examined either alone or with other chemotherapy in clinical trials in individuals with rising serum prostate-specific antigen after receiving either surgery or irradiation therapy with curative intent. © 2011 UICC.
Source Title: International Journal of Cancer
ISSN: 00207136
DOI: 10.1002/ijc.26279
Appears in Collections:Staff Publications

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