Abstract
Telmisartan, an angiotensin II receptor type 1 blocker, is often used as an antihypertension drug, and it has also been characterized as a peroxisome proliferator-activated receptor-gamma (PPARγ) ligand. The purpose of this study was to elucidate the antitumor effects of telmisartan on endometrial cancer cells. We treated three endometrial cancer cell lines with various concentrations of telmisartan, and we investigated the effects of the telmisartan on the cell proliferation, apoptosis, and their related measurements in vitro. We also administered telmisartan to nude mice with experimental tumors to determine its in vivo effects and toxicity. All three endometrial cancer cell lines were sensitive to the growth-inhibitory effect of telmisartan. The induction of apoptosis was confirmed in concert with the altered expression of genes and proteins related to the apoptosis. We also observed that DNA double-strand breaks (DSBs) were induced in HHUA (human endometrial cancer) cells by telmisartan treatment. In addition, experiments in nude mice showed that telmisartan significantly inhibited human endometrial tumor growth, without toxic side effects. Our results suggest that telmisartan might be a new therapeutic option for the treatment of endometrial cancers.
Highlights
Endometrial cancers are the most common malignant tumors of the female genital tract, and their incidence has increased in recent years [1,2]
Telmisartan functions as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPARc) ligand, activating the receptor to 25%– 30% of the maximum level achieved by the full agonists pioglitazone and resiglitazone, in which telmisartan acts independently via AT1R interaction [7]
Since we found that telmisartan could inhibit the proliferation of these cell lines, we examined the function of the antitumor effects of telmisartan through PPARc in HHUA endometrial cancer cells in vitro, using a WST-1 assay with 2-day exposure to both telmisartan at 10 or 50 mM and a PPARc antagonist, GW9662, at 10 mM
Summary
Endometrial cancers are the most common malignant tumors of the female genital tract, and their incidence has increased in recent years [1,2]. The search for agents effective in the treatment of advanced and recurrent endometrial cancers has been disappointing [2,3]. Benson et al reported a structural resemblance between telmisartan and pioglitazone, a PPARc ligand [7]. Telmisartan functions as a partial agonist of PPARc ligand, activating the receptor to 25%– 30% of the maximum level achieved by the full agonists pioglitazone and resiglitazone, in which telmisartan acts independently via AT1R interaction [7]. Telmisartan has been reported to have antiproliferative activity in prostate cancer and renal cell carcinoma [8,9,10]. The effect of telmisartan on gynecologic cancer cells has not yet been investigated
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