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Tetrac downregulates β-catenin and HMGA2 to promote the effect of resveratrol in colon cancer
- Source :
- Endocrine-related cancer. 25(3)
- Publication Year :
- 2017
-
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 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, andin 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.
- Subjects :
- 0301 basic medicine
Cancer Research
Beta-catenin
HMGA2
Endocrinology, Diabetes and Metabolism
Down-Regulation
Mice, Nude
colorectal cancer
Antineoplastic Agents
Resveratrol
resveratrol
Settore BIO/09
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Cell Line, Tumor
Animals
Humans
tetraiodothyroacetic acid
beta Catenin
Cell Proliferation
biology
Cell growth
HMGA2 Protein
Wnt signaling pathway
Drug Synergism
β-catenin
colorectal cancers
Gene Expression Regulation, Neoplastic
Thyroxine
030104 developmental biology
Oncology
chemistry
Apoptosis
030220 oncology & carcinogenesis
Catenin
Cancer cell
Colonic Neoplasms
biology.protein
Cancer research
Female
Subjects
Details
- ISSN :
- 14796821
- Volume :
- 25
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Endocrine-related cancer
- Accession number :
- edsair.doi.dedup.....5e1f25082aec53355e902c3ff12bfcb8