Effects of 1,25(OH)(2) vitamin D3 on head and neck squamous cell carcinoma cell lines

Background. Additional vitamin D receptor (VDR) mediated effects including an antiproliferative differentiation inducing influence on different benign/neoplastic cells have been discovered during the past few years for 1,25(OH)(2) D3. Methods. The influence of 1,25(OH)(2) D3 on proliferation ([H-3]-thymidine uptake/cell number) and, as determined by flow cytometry, on differentiation (cytokeratin pattern) and cell cycle distribution was studied in two cell lines (JPPA/LFFR) of squamous cell carcinomas of the head and neck (SCCHN). Results. 1,25(OH)(2) D3 (concentration 10(-7)-10(-10) M) caused a dose dependent moderate growth inhibition in both cell lines (VDR+) as reflected by reduced [H-3]-thymidine uptake and decreased cell numbers with a higher sensitivity for JP-PA cells. In both cell lines 1,25(OH)(2) D3 (10(-7) M) caused a blockade in the transition of cells from G1 to S phase, with a significant accumulation of cells in the G0/G1 phase. Changes in cytokeratin expression suggested induction of differentiation towards basal cells. Conclusion. Our results demonstrate a receptor-mediated growth inhibition and induction of differentiation by 1,25(OH)(2) D3 in human SCCHN lines.