Growth-inhibitory effect of a novel synthetic triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, on ovarian carcinoma cell lines not dependent on peroxisome proliferator-activated receptor-γ expression

Ligands for peroxisome proliferator-activated receptor γ (PPARγ) induce apoptosis and exert antiproliferative effects on several carcinoma cell lines. The present study investigates the expression of PPARγ and the possibility that agonists for PPARγ 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 PPARγ. More PPARγ was expressed in carcinoma than in adjacent normal thyroid tissue in three of six samples of human papillary carcinoma of the thyroid. PPARγ-positive thyroid carcinoma cells were treated with agonists of PPARγ, troglitazone, BRL 49653, and 15-deoxy-Δ12,14-prostaglandin J2. Troglitazone (10μ mol/L), BRL 49653 (10 μmol/L), and 15-deoxy-Δ12,14-prostaglandin J2 (1 μg/mL) decreased[ 3H]thymidine incorporation and reduced cell number, respectively, in BHP carcinoma cell lines that expressed PPARγ. Under low serum conditions, ligands for PPARγ 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 PPARγ agonist inhibit cell growth of some types of human thyroid cancer.

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Growth inhibitory effect of p21 and p53 containing adenoviruses on transitional cell carcinoma cell lines in vitro and in vivo

Urologic Oncology Seminars and Original Investigations ◽

10.1016/s1078-1439(00)00128-9 ◽

2001 ◽

Vol 6 (4) ◽

pp. 155-162 ◽

Cited By ~ 3

Author(s):

Terence W McGarvey ◽

Raymond D Meng ◽

Omari Johnson ◽

Wafik El-Deiry ◽

S.Bruce Malkowicz

Keyword(s):

Transitional Cell Carcinoma ◽

Cell Carcinoma ◽

Carcinoma Cell ◽

Transitional Cell ◽

Inhibitory Effect ◽

Growth Inhibitory Effect ◽

Carcinoma Cell Lines ◽

Growth Inhibitory

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Peroxisome proliferator–activated receptor-γ agonists cause growth arrest and apoptosis in human ovarian carcinoma cell lines

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2006.00866.x ◽

2007 ◽

Vol 17 (2) ◽

pp. 418-425 ◽

Cited By ~ 24

Author(s):

Y.-C. Yang ◽

Y.-P. Tsao ◽

T.-C. Ho ◽

I.-P Choung

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Carcinoma Cell ◽

Ovarian Cancer Cells ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Carcinoma Cell Lines ◽

Pparγ Agonists ◽

Human Ovarian Carcinoma

Peroxisome proliferator–activated receptor gamma (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. PPARγ agonists inhibit the growth of many types of cancers. To our knowledge, the effect of PPARγ agonist on ovarian tumors is not reported. In this study, we used two human ovarian carcinoma cell lines (ES-2 and PA-1) to examine the effects of the PPARγ agonists troglitazone (TGZ) and ciglitazone (CGZ) on cell survival. CGZ and TGZ inhibited viability in a dose-dependent manner in both types of ovarian cancer cells. The agonists also decreased cellular proliferation in association with an increase in the number of cells arrested in the G0/G1 phase of the cell cycle. Moreover, they increased apoptosis while increasing caspase-3 activity. Incubation of both the cell lines with the PPARγ agonists led to upregulated PPARγ expression. This effect appeared to be PPARγ independent because the PPARγ antagonist GW9662 did not reverse it. Along with the induction of apoptosis in ovarian cancer cells, protein expression levels of p53 and Bax markedly increased in response to the PPARγ agonists. Our results demonstrated that PPARγ agonists inhibited the viability of human ovarian cancer cells, at least partly by inducing apoptosis. As a result, these agonists may serve as future drugs for the prevention and treatment of ovarian cancer

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