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

Małgorzata Kapral ,  Joanna M. Wawszczyk ,  Andrzej Hollek ,  Ludmiła Węglarz 

Departament of Biochemistry, Medical University of Silesia, Narcyzow 1, Sosnowiec 41-200, Poland


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 the uncontrolled proliferation of cells. Incorrect TGF-b regulation have 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-bs exert their biological activities on various cell types including neoplastic cells via their specific receptors. In recent years, there has been a growing interest of functional foods which, besides nutrient components, contain foodstuffs that improve overall health and reduce the risk of disease. Inositol hexaphosphate (phytic acid, IP6), a phytochemical present in large amounts in legumes, cereals, oilseeds and nuts, has been reported to possess various health benefits. IP6 selectively inhibits cancer cells without affecting the normal and acts synergistically with standard therapeutics.

The aim of this study was to examine the effect of IP6 on the expression of genes encoding TGF-b1, TGF-b2, TGF-b3 isoforms and their receptors TbRI, TbRII, TbRIII 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 12h. 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-b1 mRNA was the predominant isoform in human Caco-2 cells and that IP6 enhanced transcriptional activity of genes of all three TGF-b 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, however, its higher dose (2.5 mM) caused successively increased transcript level of TGF-b isoforms and receptors with the duration of experiment up to 12 h. The findings of this study show that IP6 enhanced the genes expression of TGF-b isoforms and those of their receptors in colon cancer cells at the transcriptional level in a way dependent on its concentration and time of interaction.


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Presentation: Poster at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Małgorzata Kapral
See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2012-03-13 10:40
Revised:   2012-03-13 10:40