Prostate Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Prostate Cancer, including details on symptoms, genetics, screening, treatment, information.

Mechanistic and pharmacodynamic studies of a 25-hydroxyvitamin D3 derivative in prostate cancer cells.

Lambert JR, Young CD, Persons KS, Ray R

Department of Pathology, University of Colorado Health Science Center, Aurora, CO, USA.

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the biologically active form of vitamin D has strong antiproliferative effects in cancer cells. But it is highly toxic at therapeutic doses. We have observed that 25-hydroxyvitamin D(3)-3-bromoacetate (25-OH-D(3)-3-BE), a derivative of 25-hydroxyvitamin D(3), the pro-hormonal form of 1,25(OH)(2)D(3) has strong growth-inhibitory and proapoptotic properties in hormone-sensitive and hormone-refractory prostate cancer cells. In the present investigation we demonstrate that the antiproliferative effect of 25-OH-D(3)-3-BE is predominantly mediated by VDR in ALVA-31 prostate cancer cells. In other mechanistic studies we show that the proapoptotic property of 25-OH-D(3)-3-BE is related to the inhibition of phosphorylation of Akt, a pro-survival protein. Furthermore, we carried out cellular uptake and serum stability studies of 25-OH-D(3)-3-BE to demonstrate potential therapeutic applicability of 25-OH-D(3)-3-BE in hormone-sensitive and hormone-insensitive prostate cancer.

Published 1 August 2007 in Biochem Biophys Res Commun, 361(1): 189-95.
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