Tetrac downregulates ß-catenin and HMGA2 to promote the effect of resveratrol in colon cancer.
Endocr Relat Cancer
; 25(3): 279-293, 2018 03.
Article
in En
| MEDLINE
| ID: mdl-29255096
ABSTRACT
The molecular pathogenesis of colorectal cancer encompasses the activation of several oncogenic signaling pathways that include the Wnt/ß-catenin pathway and the overexpression of high mobility group protein A2 (HMGA2). Resveratrol - the polyphenolic phytoalexin - binds to integrin αvß3 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 ß-catenin and HMGA2, which are capable of compromising resveratrol-induced COX-2 nuclear translocation. Silencing of either ß-catenin or HMGA2 promoted resveratrol-induced anti-proliferation and COX-2 nuclear accumulation which is essential for integrin αvß3-mediated-resveratrol-induced apoptosis in cancer cells. Concurrently, tetrac enhanced nuclear abundance of chibby family member 1, the nuclear ß-catenin antagonist, which may further compromise the nuclear ß-catenin-dependent gene expression and proliferation. Taken together, these results suggest that tetrac targets ß-catenin and HMGA2 to promote resveratrol-induced-anti-proliferation in colon cancers, highlighting its potential in anti-cancer combination therapy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thyroxine
/
Colonic Neoplasms
/
HMGA2 Protein
/
Beta Catenin
/
Resveratrol
/
Antineoplastic Agents
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Endocr Relat Cancer
Journal subject:
ENDOCRINOLOGIA
/
NEOPLASIAS
Year:
2018
Document type:
Article
Affiliation country:
Taiwan