Ligands for
peroxisome proliferator-activated receptor gamma (
PPARgamma) induce apoptosis and exert antiproliferative effects on several
carcinoma cell lines. The present study investigates the expression of
PPARgamma and the possibility that agonists for
PPARgamma also inhibit the growth of human
thyroid carcinoma cells. We examined this hypothesis using six cell lines, designated BHP
thyroid carcinoma cells, which originated from patients with
papillary thyroid carcinoma. RT-PCR analysis revealed that the
thyroid carcinoma cell lines BHP2-7, 7-13, 10-3, and 18-21 express
PPARgamma. More
PPARgamma was expressed in
carcinoma than in adjacent normal thyroid tissue in three of six samples of human
papillary carcinoma of the thyroid.
PPARgamma-positive
thyroid carcinoma cells were treated with agonists of
PPARgamma,
troglitazone,
BRL 49653, and
15-deoxy-12,14-prostaglandin J2.
Troglitazone (10 micromol/L),
BRL 49653 (10 micromol/L), and
15-deoxy-12,14-prostaglandin J2 (1 microg/mL) decreased [(3)H]
thymidine incorporation and reduced cell number, respectively, in BHP
carcinoma cell lines that expressed
PPARgamma. Under low serum conditions,
ligands for
PPARgamma induced condensation of the nucleus and fragmentation of
chromatin into
nucleosome ladders. These findings indicate that the death of
thyroid carcinoma cells is a form of apoptosis. To investigate the molecular mechanism of the apoptosis, we assessed expression of the apoptosis-regulatory genes bcl-2, bax, and c-myc.
Troglitazone significantly increased the expression of c-myc
messenger RNA but had no effect on the expression of bcl-2 and bax in
thyroid carcinoma cells. These results suggest that, at least in part, the induction of apoptosis in human
papillary thyroid carcinoma cells may be due to an increase of c-myc.
Troglitazone (500 mg/kg.day) significantly inhibited
tumor growth and prevented distant
metastasis of BHP18-21
tumors in nude mice in vivo. Taken together, these results suggest that
PPARgamma agonist inhibit cell growth of some types of human
thyroid cancer.