calcitriol and Stomach-Neoplasms

It has been previously demonstrated that vitamin D acts as a prognostic indicator of gastric cancer and may be correlated with the incidence risk of gastric cancer. However, the effect of 1,25-dihydroxyvitamin D3 on the apoptosis of human gastric cancer cells is unclear. The aim of this study was to determine whether 1,25-dihydroxyvitamin D3 induced the cellular apoptosis of BGC-823 gastric cancer cells and to determine the potential mechanism of action.. We demonstrate that 1,25-dihydroxyvitamin D3 induced the apoptosis of gastric cancer cells via the processing of PARP and cleavage of caspase 3. Additionally, an increase in BAX expression and a decrease in ERK1/2 and AKT phosphorylation were associated with 1,25-dihydroxyvitamin D3-induced apoptosis. The mRNA expression levels of VDR, CYP24A1, and p21 were increased significantly following 1,25-dihydroxyvitamin D3 treatment.. These findings suggest that 1,25-dihydroxyvitamin D3 exerts tumor-suppressive effects on BGC-823 human gastric cancer cells.

Topics: Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Cyclin-Dependent Kinase Inhibitor p21; Humans; In Vitro Techniques; MAP Kinase Signaling System; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptors, Calcitriol; Reverse Transcriptase Polymerase Chain Reaction; Steroid Hydroxylases; Stomach Neoplasms; Tumor Cells, Cultured; Vitamin D; Vitamin D3 24-Hydroxylase

Previous studies have shown an anticancer effect of vitamin D, but the mechanisms underlying this action have not been fully explored. Here we show that 1,25-dihydroxyvitamin D3 (VD3, the active form of vitamin D) significantly promoted apoptosis in the undifferentiated gastric cancer cell line HGC-27, and this was accompanied by a concurrent increase in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression on VD3 treatment. In contrast, knockdown of PTEN expression by stable transfection of PTEN small interfering RNA greatly decreased the apoptosis rate. We further demonstrated that VD3 induced PTEN expression through vitamin D receptor. In addition, our evidence showed that vitamin D receptor, Egr-1 and p300 induced PTEN expression in a synergistic fashion. Furthermore, we found that the histone deacetylase inhibitors trichostatin A and sodium butyrate and the methylation inhibitor 5-aza-2'-deoxycytidine played important roles in vitamin D-induced apoptosis through PTEN upregulation. The data presented in this article suggest potential benefits of vitamin D in gastric cancer therapies in association with the use of trichostatin A/sodium butyrate and 5-aza-2'-deoxycytidine.

Topics: Acetylation; Apoptosis; Azacitidine; Butyrates; Cell Line, Tumor; Decitabine; Early Growth Response Protein 1; Gene Knockdown Techniques; Histones; Humans; Hydroxamic Acids; p300-CBP Transcription Factors; Promoter Regions, Genetic; PTEN Phosphohydrolase; Stomach Neoplasms; Up-Regulation; Vitamin D