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 cellsviacyclooxygenase 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, andin vivoThe 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.

Nana, A.w., Chin, Y., Lin, C., Ho, Y., Bennett, J.a., Shih, Y., et al. (2018). Tetrac downregulates β-catenin and HMGA2 to promote the effect of resveratrol in colon cancer. ENDOCRINE-RELATED CANCER, 25(3), 279-293-293 [10.1530/ERC-17-0450].

Tetrac downregulates β-catenin and HMGA2 to promote the effect of resveratrol in colon cancer

Pedersen, Jens Z;
2018-03

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 cellsviacyclooxygenase 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, andin vivoThe 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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/09
English
Con Impact Factor ISI
HMGA2; colorectal cancers; resveratrol; tetraiodothyroacetic acid; β-catenin
Nana, A.w., Chin, Y., Lin, C., Ho, Y., Bennett, J.a., Shih, Y., et al. (2018). Tetrac downregulates β-catenin and HMGA2 to promote the effect of resveratrol in colon cancer. ENDOCRINE-RELATED CANCER, 25(3), 279-293-293 [10.1530/ERC-17-0450].
Nana, Aw; Chin, Y; Lin, C; Ho, Y; Bennett, Ja; Shih, Y; Chen, Y; Changou, Ca; Pedersen, Jz; Incerpi, S; Liu, Lf; Whang-Peng, J; Fu, E; Li, W; Mousa, Sa; Lin, H; Davis, Pj
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/193238
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