Inhibition of CYP27B1 and CYP24 Increases the Anti-proliferative Effects of 25-Hydroxyvitamin D3in LNCaP Cells
Artikel i vetenskaplig tidskrift, 2021

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)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.

25-hydroxyvitamin D 3

Vitamin D

Cell proliferation

VDR

Prostate cancer

PDIA3

Genistein

Författare

S. Karlsson

Jönköping University

Maria Araceli Diaz Cruz

Jönköping University

Maria Faresjö

Chalmers, Biologi och bioteknik

Athanasia Papadopoulou Khamou

Sahlgrenska universitetssjukhuset

Dennis Larsson

Sahlgrenska universitetssjukhuset

Anticancer Research

0250-7005 (ISSN)

Vol. 41 10 4733-4740

Ämneskategorier

Cellbiologi

Cell- och molekylärbiologi

Farmakologi och toxikologi

DOI

10.21873/anticanres.15288

Mer information

Senast uppdaterat

2021-10-19