Effects of 1alpha, 25-dihydroxyvitamin D-3 on programmed cell death of Ishikawa endometrial cancer cells through ezrin phosphorylation

Abstract

This study investigated the effects of 1, 25-dihydroxyvitamin D-3-induced cell death and its underlying molecular mechanisms in Ishikawa endometrial carcinoma cells. The effects of 1, 25-dihydroxyvitamin D-3 on Ishikawa cells were examined by 3-[4,5-dimethylthiazol-2-yl]-2.5-diphenyl-tetrazolium bromide, thiazolyl blue (MTT) assay. 1, 25-dihydroxyvitamin D-3 was shown to induce programmed cell death in Ishikawa endometrial carcinoma cells by activation of caspase-3 and caspase-9, along with elevation of Bcl-2 and Bcl-xL. Cell viability was reduced by 1, 25-dihydroxyvitamin D-3 in a concentration-dependent manner up to 2.5M. In addition, ezrin phosphorylation increased with the 1, 25-dihydroxyvitamin D-3 concentration (0-0.5M). The protein level of caspase-9 was increased by 1, 25-dihydroxyvitamin D-3 up to 0.5M. This is the first report regarding the efficacy and molecular mechanisms underlying the effects of 1, 25-dihydroxyvitamin D-3 in endometrial cancer cells. Our findings indicate that 1, 25-dihydroxyvitamin D-3 induces endometrial cancer cell death in a concentration-dependent manner.Impact statementUp to date, there is no report about the efficacy and molecular underlying mechanisms on the effect of vitamin D-3 in endometrial cancer cells. Our findings indicate that 1, 25-dihydroxyvitamin D-3. which is an active metabolite of vitamin D-3, induces Ishikawa endometrial cancer cell death in a concentration-dependent manner by activation of caspase-3 and -9, along with elevation of Bcl-2 and Bcl-xL. In addition, the same concentration of 1, 25-dihydroxyvitamin D-3 that provoked apoptotic signals caused phosphorylation of ezrin at threonine 567 in a VDR-dependent manner. This study suggests that 1, 25-dihydroxyvitamin D-3 within the optimal range (0.5 uM) would induce apoptosis through Fas-ezrin-caspase-3, -8, -9 signalling axis which may be a critical cell death regulator in Ishikawa endometrial cancer cell. Further study will be more interesting to address molecular connections or prove this critical optimal concentration range of vitamin D.