Antiproliferative effects of the biologically active metabolite of vitamin D3 (1,25 [OH](2) D-3) on head and neck squamous cell carcinoma cell lines

In addition to a role in calcium and phosphate homeostasis other vitamin D receptor (VDR) mediated effects have been discovered during the past few years for the biologically active metabolite of vitamin D, 1,25(OH)(2)D-3. An antiproliferative, differentiation-inducing effect on nonmalignant and neoplastic cells of different origin has now been described. We examined the influence of 1,25(OH)(2)D-3 on human squamous cell carcinomas of the head and neck (SCCHN). A differentiated (JP-PA) and undifferentiated (LF-FR) SCCHN line was studied with respect to proliferative capacity (using [H-3]-thymidine uptake and cell number) and cell cycle distribution as determined by flow cytometry (FAGS). Both cell lines were positive for VDR, which was found to be increased after the addition of 10(-7) M 1,25(OH)(2)D-3, as shown by FAGS analyses. The administration of 1,25(OH)(2)D-3 at a concentration between 10(-7) M and 10(-10) M caused a dose-dependent moderate growth inhibition, as reflected by down-regulation of DNA synthesis (reduced [H-3]-thymidine uptake) and a decrease in cell numbers. The JP-PA cell line showed a significant growth reduction for both concentrations tested, whereas for LF-FR a significant inhibition was detected only for 10(-7) M. The addition of 10(-7) M 1,25(OH)(2)D-3 caused a blockade in the transition of cells from G1 to S phase in both cell lines, with a significant accumulation of cells in the G0/G1 phase. Our results demonstrate a receptor-mediated, dose-dependent inhibition of neoplastic growth by 1,25(OH)(2)D-3 in human SCCHN lines.