Vitamin D stimulates apoptosis in gastric cancer cells in synergy with trichostatin A /sodium butyrate-induced and 5-aza-2'-deoxycytidine-induced PTEN upregulation.
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.
Pan
Lina
L
The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
Matloob
Ammar F
AF
Du
Juan
J
Pan
Hong
H
Dong
Zhixiong
Z
Zhao
Jing
J
Feng
Yu
Y
Zhong
Yun
Y
Huang
Baiqu
B
Lu
Jun
J
D000107:Acetylation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D045744:Cell Line, Tumor; D000077209:Decitabine; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D001374:Azacitidine; D002087:Butyrates; D000077209:Decitabine; D051766:Early Growth Response Protein 1; D006657:Histones; D006877:Hydroxamic Acids; D051059:PTEN Phosphohydrolase; D014807:Vitamin D; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C012589:trichostatin A; C097949:1,25-dihydroxyvitamin D