title: Telmisartan induces growth inhibition, DNA double-strand breaks and apoptosis in human endometrial cancer cells.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Koyama
authors.affiliation: Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishida
authors.affiliation: Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Terukazu
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Toshie
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Furukawa
authors.affiliation: Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Oita, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narahara
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D000077333:Telmisartan; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D001565:Benzoates; D000077333:Telmisartan