Tetrac downregulates {beta}-catenin and HMGA2 to promote the effect of resveratrol in colon cancer

The molecular pathogenesis of colorectal cancer encompasses the activation of several oncogenic signaling pathways that include the Wnt/β-catenin pathway and the overexpression of high mobility group protein A2 (HMGA2). Resveratrol – the polyphenolic phytoalexin – binds to integrin αvβ3 to induce apoptosis in cancer cells via cyclooxygenase 2 (COX-2) nuclear accumulation and p53-dependent apoptosis. Tetraiodothyroacetic acid (tetrac) is a de-aminated derivative of l-thyroxine (T4), which – in contrast to the parental hormone – impairs cancer cell proliferation. In the current study, we found that tetrac promoted resveratrol-induced anti-proliferation in colon cancer cell lines, in primary cultures of colon cancer cells, and in vivo. The mechanisms implicated in this action involved the downregulation of nuclear β-catenin and HMGA2, which are capable of compromising resveratrol-induced COX-2 nuclear translocation. Silencing of either β-catenin or HMGA2 promoted resveratrol-induced anti-proliferation and COX-2 nuclear accumulation which is essential for integrin αvβ3-mediated-resveratrol-induced apoptosis in cancer cells. Concurrently, tetrac enhanced nuclear abundance of chibby family member 1, the nuclear β-catenin antagonist, which may further compromise the nuclear β-catenin-dependent gene expression and proliferation. Taken together, these results suggest that tetrac targets β-catenin and HMGA2 to ...

Source: Endocrine-Related Cancer - February 7, 2018 Category: Endocrinology Authors: Nana, A. W., Chin, Y.-T., Lin, C.-Y., Ho, Y., Bennett, J. A., Shih, Y.-J., Chen, Y.-R., Changou, C. A., Pedersen, J. Z., Incerpi, S., Liu, L. F., Whang-Peng, J., Fu, E., Li, W.-S., Mousa, S. A., Lin, H.-Y., Davis, P. J. Tags: Research Source Type: research