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- Title
Vitamin D stimulates apoptosis in gastric cancer cells in synergy with trichostatin A /sodium butyrate-induced and 5-aza-2′-deoxycytidine-induced PTEN upregulation.
- Authors
Lina Pan; Matloob, Ammar F.; Juan Du; Hong Pan; Zhixiong Dong; Jing Zhao; Yu Feng; Yun Zhong; Baiqu Huang; Jun Lu
- Abstract
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. Structured digital abstract • , , : P300 (uniprotkb: ) physically interacts ( ) with VDR (uniprotkb: ) and EGR1 (uniprotkb: ) by anti bait coimmunoprecipitation ( )
- Subjects
VITAMIN D; CANCER cells; CELL lines; APOPTOSIS; RNA
- Publication
FEBS Journal, 2010, Vol 277, Issue 4, p989
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2009.07542.x