Inhibition of CYP27B1 and CYP24 Increases the Anti-proliferative Effects of 25-Hydroxyvitamin D3in LNCaP Cells

• Published in: Anticancer research 2021-10, Vol.41 (10), p.4733
• Main Authors: Karlsson, Sandra, Diaz Cruz, Maria Araceli, Faresjö, M., Khamou, A. P., Larsson, D.
• Format: Article
• Language: English
• Subjects: 25-hydroxyvitamin D3; Cell proliferation; Genistein; PDIA3; Prostate cancer; VDR; Vitamin D
• ISSN: 1791-7530; 0250-7005
• DOI: 10.21873/anticanres.15288

Background/Aim: Growing evidence suggests that vitamin D3exerts 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)D3on 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)D3inhibited cell proliferation in a dose- and time-dependent manner. The inhibitory effect of 25(OH)D3on cell proliferation was potentiated after inhibition of CYP17B1 and CYP24 by genistein, preventing further metabolism of 25(OH)D3to 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)D3has a direct inhibitory effect on cell proliferation, which is enhanced and accelerated when the metabolism of 25(OH)D3to 1,25(OH)2D3and 24,25(OH)2D3was inhibited by the CYP17B1 and CYP24 inhibitor genistein. Furthermore, treatment with 25(OH)D3increased receptor transcript expression, suggesting an increased VDR stability and sensibility of the treated cells.