Inhibition of CYP27B1 and CYP24 Increases the Anti-proliferative Effects of 25-Hydroxyvitamin D in LNCaP Cells.

Background/aim: Growing evidence suggests that vitamin D exerts anticancer effects. The present study aimed to evaluate 25-hydroxyvitamin D (25(OH)D) as a potential endocrine factor regulating proliferation and vitamin D receptor expression in LNCaP prostate cancer cells.

Materials And Methods: Cell counting after treatment was utilized to assess the effect of 25(OH)D on cell proliferation. Changes in mRNA expression of the vitamin D receptors, VDR and PDIA3, were evaluated using droplet digital polymerase chain reaction (ddPCR).

Results: 25(OH)D inhibited cell proliferation in a dose- and time-dependent manner. The inhibitory effect of 25(OH)D on cell proliferation was potentiated after inhibition of CYP17B1 and CYP24 by genistein, preventing further metabolism of 25(OH)D to 1,25-dihydroxyvitamin D (1,25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)D). Expression of PDIA3 and VDR mRNA increased after treatment with 25(OH)D, whereas the ratio between PDIA3 and VDR mRNA remained unchanged.

Conclusion: 25(OH)D has a direct inhibitory effect on cell proliferation, which is enhanced and accelerated when the metabolism of 25(OH)D to 1,25(OH)D and 24,25(OH)D was inhibited by the CYP17B1 and CYP24 inhibitor genistein. Furthermore, treatment with 25(OH)D increased receptor transcript expression, suggesting an increased VDR stability and sensibility of the treated cells.