Induction of the expression of genes encoding tgf-β isoforms and their receptors by inositol hexaphosphate in human colon cancer cells

摘要

Transforming growth factors-β (TGF-β) are multifunctional cytokines involved in the regulation of cell development, differentiation, survival and apoptosis. They are also potent anticancer agents that inhibit uncontrolled proliferation of cells. Incorrect TGF-β regulation has been implicated in the pathogenesis of many diseases including inflammation and cancer. In humans, the TGF-β family consists of three members (TGF-β1, 2, 3) that show high similarity and homology. TGF-βs exert biological activities on various cell types including neoplastic cells via their specific receptors. Inositol hexaphosphate (phytic acid, IP6), a phytochemical has been reported to possess various health benefits. The aim of this study was to examine the effect of IP6 on the expression of genes encoding TGF-β1, TGF-β2, TGF-β3 isoforms and their receptors TβRI, TβRII, TβRIII in human colorectal cancer cell line Caco-2. The cells were treated with 0.5, 1 and 2.5 mM IP6 for 3, 6 and 12 h. The untreated Caco-2 cells were used as the control. Quantification of genes expression was performed by real time QRT-PCR technique with a SYBR Green I chemistry. The experimental data revealed that the TGF-β1 mRNA was the predominant isoform in Caco-2 cells and that IP6 enhanced transcriptional activity of genes of all three TGF-β isoforms and their receptors TβRI, TβRII TβRIII in these cells. At concentrations up to 1 mM, IP6 over-expressed the genes in 6 h lasting cultures, and its higher dose (2.5 mM) caused successively increasing transcript level of TGF-β isoforms and receptors with the duration of experiment up to 12 h. The findings of this study indicate that one of anti-cancer abilities of IP6 can be realized by enhancing the gene expression of TGF-β isoforms and their receptors at the transcriptional level.