Mol Med Rep. 2016 Feb;13(2):1373-80. doi: 10.3892/mmr.2015.4676. Epub 2015 Dec 11.

1,25(OH)2D3 inhibits the progression of hepatocellular carcinoma via downregulating HDAC2 and upregulating P21(WAFI/CIP1).

by Huang J1, Yang G2, Huang Y3, Kong W1, Zhang S2.

Abstract

Vitamin D, termed 1,25(OH)2D3 in it’s active form, activity is associated with a reduced risk of hepatocellular carcinoma (HCC) and is an important immune regulator. However, the detail molecular mechanisms underlying the effects of 1,25(OH)2D3 on the progression of HCC are widely unknown. Histone deacetwylase 2 (HDAC2) is usually expressed at high levels in tumors, and its downregulation leads to highexpression levels of cell cycle components, including p21(WAF1/Cip1), a well-characterized modulator, which is critical in cell senescence and apoptosis. The present study investigated whether vitamin Dinhibits HCC via the regulation of HDAC2 and p21(WAF1/Cip1). Firstly, the toxic concentrations of 1,25(OH)2D3 were determined, according to trypan blue and [(3)H]thymidine incorporation assays. Secondly, HCC cells lines were treated with different concentrations of 1,25(OH)2D3. The expression of HDAC2 was either silenced via short hairpin (sh)RNA or induced by transfection of plasmids expressing the HDAC2 gene in certain HCC cells. Finally the mRNA and protein levels of HDAC2 and p21(WAF1/Cip1) were measured using reverse transcription-quantitative polymerase chain reaction and western blot analyses. The results revealed that 1,25(OH)2D3 treatment reduced the expression of HDAC2 and increased the expression of p21(WAF1/Cip1), in a dose-dependent manner, resulting in the reduction of HCC growth. Elevated levels of HDAC2 reduced the expression of p21(WAF1/Cip1), resulting in an increase in HCC growth. HDAC2 shRNA increased the expression of p21(WAF1/Cip1), resulting in reduction in HCC growth. Thus, 1,25(OH)2D3 exerted antitumorigenic effects through decreasing the expression levels of HDAC2 and increasing the expression of p21(WAF1/Cip1), which inhibited the development of HCC and may indicate the possible underlying mechanism. These results suggest that vitamin D3 may be developed as a potential drug for effective therapy in the treatment of HCC.

Jeff T Bowles: Being the author of the best-selling book on Vitamin D3 in the world, and given the topic of the book was the miraculous results of my one year experiment of taking HIGH DOSES of vitamin D3, puts me in the unique position of being the sounding board for many hundreds if not a few thousands of others who have embarked on their own high dose vitamin d3 experiment. Nobody on planet earth has this amount of unusual and exciting knowledge, and I will be sharing it with you in this series of 100 short articles describing a disease and some sort of amazing result achieved with high dose D3 therapy.

Sincerely Jeff T. Bowles