Selective thyroid hormone receptor beta agonist, GC-1, is capable to reduce growth of colorectal tumor in syngeneic mouse models.

Abstract

OBJECTIVE:

The effect of thyroid hormone (TH) on cancers was proposed more than 100 years ago; however, conclusions are conflicting. THs are precisely regulated at tissue and cellular levels. It seems that this regulation is altered in cancers. Thyroid hormone receptor beta (TRβ) has anti-proliferative and tumor-suppressive effects in many cancer cells. Therefore, we decided to investigate thyroid hormone receptor beta (THRB) expression and activation by the selective agonist, GC-1, on tumor growth in a syngeneic mouse model of colorectal cancer (CRC) and colon cell lines.

METHODS:

In vitro cell viability assay using MTT analysis, cell cycle analysis by PI staining, and FACS analysis were performed. In vivo tumor growth measurements were carried out by caliper and [18F] Fluoro-2-deoxy-2-D-glucose (FDG) - PET imaging. Gene expressions were determined using quantitative-PCR.

RESULTS:

Some concentrations of GC-1 had a marked negative effect on the cell viability of colorectal cell lines. Cell cycle analysis showed that the anti-proliferative effect of GC-1 may not result from cell cycle arrest or apoptosis. Tumor growth analysis in mice harboring colorectal tumor showed that GC-1 treatment for 8 d profoundly inhibited tumor growth and 18FDG uptake. THRB expression was decreased in mice tumor; however, it was upregulated following GC-1 administration.

CONCLUSIONS:

Our results showed that specific activation of TRβ by GC-1 had negative effect on tumor growth and restored its gene expression in tumors of CRC mice model.

• Authors: Katayoun Pourvali, Ghazaleh Shimi, Arman Ghorbani, Azam Shakery, Farshad Hosseini Shirazi, Hamid Zand
• Journal: Journal of receptor and signal transduction research (J Recept Signal Transduct Res) Vol. 42 Issue 5 Pg. 495-502 (Oct 2022) ISSN: 1532-4281 [Electronic] England
• PMID: 35473566 (Publication Type: Journal Article)

Chemical References

• Acetates
• GC 1 compound
• Phenols
• Thyroid Hormone Receptors beta
• Thyroid Hormones
• Fluorodeoxyglucose F18
• Glucose

Topics

• Acetates
• Animals
• Colorectal Neoplasms (drug therapy, genetics)
• Disease Models, Animal
• Fluorodeoxyglucose F18
• Glucose
• Mice
• Phenols
• Thyroid Hormone Receptors beta (genetics, metabolism)
• Thyroid Hormones