Korean J Endocr Surg. 2003 Oct;3(2):113-120. Korean.
Published online Oct 31, 2003.
Copyright © 2003 Korean Association of Thyroid and Endocrine Surgeons; KATES
Original Article

Troglitazone Increases the Susceptibility to TRAIL-Induced Apoptosis in Thyroid Cancer Cell Lines

Jin-Woo Park, M.D. and Orlo H. Clark1
    • Department of Surgery, Chungbuk National University, Cheongju, Korea.
    • 1Department of Surgery, University of California, San Francisco, UCSF/Mount Zion Medical Center, San Francisco, USA.
Accepted September 18, 2003.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induces apoptosis in many human cancer cells but not in normal cells. Thyroid cancer cells, however, appear to be relatively resistant to TRAIL-induced apoptosis. We investigated the effect of troglitazone, a PPARγ agonist, on TRAIL-induced apoptosis in thyroid cancer cells.

Methods

We used 6 thyroid cancer cell lines: TPC-1, FTC- 133, FTC-236, FTC-238, XTC-1, and ARO82-1. We used flow cytometry to detect apoptosis and used MTT assay to measure anti-proliferation effects. ANOVA was used for statistical analysis.

Results

TPC-1 cells were the most sensitive to soluble TRAIL. FTC-133 and ARO82-1 were resistant to TRAIL and growth inhibition was less than 20% at concentration of 800 ng/ml of TRAIL. In both TPC-1 (TRAIL-sensitive) and FTC- 133 (TRAIL-resistant) thyroid cancer cell lines, pretreatment with troglitazone enhanced TRAIL-induced cell death significantly. Bcl-family proteins did not seem to be involved in sensitization of TRAIL-induced apoptosis by troglitazone.

Conclusion

TRAIL in combination with troglitazone induces apoptosis in thyroid cancer cells at suboptimal concentrations that can not be achieved using TRAIL alone.

Keywords
TRAIL; Apoptosis; PPARγ; Thyroid cancer


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