The efficacy of the vitamin D metabolite, 25-hydroxyvitamin D3 as a chemopreventive agent has already been implicated in colon cancer. In a... Show moreThe efficacy of the vitamin D metabolite, 25-hydroxyvitamin D3 as a chemopreventive agent has already been implicated in colon cancer. In a microarray analysis data from our laboratory, 25D3 treatment upregulated TIMP-2 mRNA expression in human colon cancer cells. TIMP-2 is a multifunctional protein affecting cell migration, cell growth and differentiation, anti-angiogenesis, pro and anti – apoptosis, and synaptic plasticity of cells. In this study we characterized the TIMP-2 expression with the treatment of 25-Hydroxyvitamin D3, in colon cancer cells. We found that TIMP-2 was significantly upregulated at transcriptional, translational and post translational level when treated with 500nM 25D3, in several human colon cancer cell lines HT29, Caco2, SW620, but was not regulated in SW480. Concomitantly, the cell proliferation was significantly inhibited by different concentrations (250nM, 500nM and 100nM) of 25D3 treatment for 7days in Caco2 and HT29, but not in SW480. Similarly, cell invasion and cell migration were also significantly inhibited in HT29 cells, but not in SW480 when conditioned media generated from treatment of HT29 and SW480 cells with 500nM 25D3 for 72 , were used as chemoattractant. These results suggested that TIMP-2 present in the conditioned media from 25D3 treated HT29 cells inhibited the invasive and metastatic abilities of the human colon cancer cell line. This data was also supported in the in vivo mice experiment, in which the lung metastasis of mice colon adenocarcinoma cells, CT26 was inhibited by 25% (p=0.01), when pre-treated with 25D3 (500mg/kg). At the same time, the TIMP-2 levels were also higher in the 25D3 treated groups. M.S. in Biology, December 2011 Show less
