Tetrac downregulates β-catenin and HMGA2 to promote the effect of resveratrol in colon cancer. Issue 3 (March 2018)

• Record Type: Journal Article
• Authors: Nana, André Wendindondé; Chin, Yu-Tang; Lin, Chi-Yu; Ho, Yih; Bennett, James A; Shih, Ya-Jung; Chen, Yi-Ru; Changou, Chun A; Pedersen, Jens Z; Incerpi, Sandra; Liu, Leroy F; Whang-Peng, Jacqueline; Fu, Earl; Li, Wen-Shan; Mousa, Shaker A; Lin, Hung-Yun; Davis, Paul J
• Is Part Of: Endocrine-related cancer. Volume 25:Issue 3(2018)
• Page Start: 279
• Page End: 293
• Publication Date: 2018-03
• Subjects: tetraiodothyroacetic acid -- resveratrol -- β-catenin -- HMGA2 -- colorectal cancers; Endocrine glands -- Cancer -- Periodicals; Endocrinology -- Periodicals; Cancer -- Endocrine aspects -- Periodicals; 616.9944005
• DOI: 10.1530/ERC-17-0450
• Languages: English
• ISSNs: 1351-0088

Abstract

Abstract : 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 ofl -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 promote resveratrol-induced-anti-proliferation in colon cancers, highlighting its potential in anti-cancer combination therapy.