Combinational Effects of Vitamin D3and Retinoic Acid (Alltransand 9cis) on Proliferation, Differentiation, and Programmed Cell Death in Two Small Cell Lung Carcinoma Cell Lines

Abstract The effects of a combination of vitamin D 3 [1,25(OH) 2 D 3 ] and retinoic acid (RA) on proliferation, differentiation, and apoptosis of the human small cell lung carcinoma (SCLC) cell lines NCI-H82 and NCI-H209 were evaluated. Cell proliferation was inhibited by 1,25(OH) 2 D 3 and RA alone. The combination of 1,25(OH) 2 D 3 and the cis form of retinoic acid resulted in an additive decrease in cell proliferation and the induction of apoptosis in various concentrations. Moreover, 3 H-thymidine incorporation was inhibited and the number of viable cells was decreased. The characteristics of the apoptotic cells were examined and confirmed by morphologic analysis, light and electron microscopy, and fluorescence detection. It was concluded that 1,25(OH) 2 D 3 and RA exert additive effects on the inhibition of proliferation and the induction of apoptosis in both the NCI-H82 and the NCI-H209 SCLC cell lines. This finding has important implications for the use of retinoids and 1,25(OH) 2 D 3 in cancer prevention and in the therapy of small cell lung carcinoma.