Inhibition of CYP27B1 and CYP24 Increases the Anti-proliferative Effects of 25-Hydroxyvitamin D₃ in LNCaP Cells

Background/aim: Growing evidence suggests that vitamin D₃ exerts anticancer effects. The present study aimed to evaluate 25-hydroxyvitamin D₃ (25(OH)D₃) 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)D₃ 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)D₃ inhibited cell proliferation in a dose- and time-dependent manner. The inhibitory effect of 25(OH)D₃ on cell proliferation was potentiated after inhibition of CYP17B1 and CYP24 by genistein, preventing further metabolism of 25(OH)D₃ to 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) and 24,25-dihydroxyvitamin D₃ (24,25(OH)₂D₃). Expression of PDIA3 and VDR mRNA increased after treatment with 25(OH)D₃, whereas the ratio between PDIA3 and VDR mRNA remained unchanged.

Conclusion: 25(OH)D₃ has a direct inhibitory effect on cell proliferation, which is enhanced and accelerated when the metabolism of 25(OH)D₃ to 1,25(OH)₂D₃ and 24,25(OH)₂D₃ was inhibited by the CYP17B1 and CYP24 inhibitor genistein. Furthermore, treatment with 25(OH)D₃ increased receptor transcript expression, suggesting an increased VDR stability and sensibility of the treated cells.