Introduction: Prostate cancer (PCa) is the most commonly diagnosed non-skin malignancy among men. The recent studies suggest an important role of vitamin D in prevention prostate cancer. Androgens seem to be involved also in the protective effect of vitamin D against PCa, interacting with VDR receptor and other molecular mechanisms that increase the calcitriol protective effect in prostate.
Aim: To review the literature from the last 5 years about the molecular mechanisms of vitamin D and androgens related to PCa.
Materials and Methods: The MEDLINE database of references and abstracts on life sciences and biomedical topics was used. The data from 155 articles were analyzed for this review.
Results: The results show that vitamin D exerts protective effect against PCa by different mechanisms: cell cycle arrest/inhibition in G1/S phase; activation of pro-apoptotic genes that induce cell apoptosis; anti-inflammatory effect due to its inhibitory effect on cyclooxygenase-2; blockage the angiogenesis by decreasing the vascular endothelial growth factor, and stopping the invasion and metastasis decreasing the α6 and β4 integrins. Androgens promote the growth and regulation of normal prostate cells activating genes related to lipogenesis, thus providing phospholipids for prostate cell membranes. On the other hand there are data showing that calcitriol regulates genes encoding enzymes of lipogenesis including fatty acid biosynthesis. Fatty acid synthase (FAS) was found to be down-regulated by calcitriol. The findings suggest that FAS is involved in the antiproliferative effect of calcitriol in presence of androgens on prostate cancer cells. There are also evidences for interaction between the signaling pathways of calcitriol and androgens.
Conclusions: Further studies need to be done to clarify the molecular mechanisms by which both calcitriol and androgens are involved in PCa development/protection.
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