Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T‐cell leukemia cells. Issue 5 (13th April 2016)

• Record Type: Journal Article
• Authors: Kozako, Tomohiro; Soeda, Shuhei; Yoshimitsu, Makoto; Arima, Naomichi; Kuroki, Ayako; Hirata, Shinya; Tanaka, Hiroaki; Imakyure, Osamu; Tone, Nanako; Honda, Shin‐ichiro; Soeda, Shinji
• Is Part Of: FEBS open bio. Volume 6:Issue 5(2016)
• Page Start: 442
• Page End: 460
• Publication Date: 2016-04-13
• Subjects: adult T‐cell leukemia/lymphoma -- apoptosis -- autophagy -- drug repositioning -- human T‐cell leukemia virus‐1 -- telmisartan; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12055
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : Adult T‐cell leukemia/lymphoma (ATL), an aggressive T‐cell malignancy that develops after long‐term infection with human T‐cell leukemia virus (HTLV‐1), requires new treatments. Drug repositioning, reuse of a drug previously approved for the treatment of another condition to treat ATL, offers the possibility of reduced time and risk. Among clinically available angiotensin II receptor blockers, telmisartan is well known for its unique ability to activate peroxisome proliferator‐activated receptor‐γ, which plays various roles in lipid metabolism, cellular differentiation, and apoptosis. Here, telmisartan reduced cell viability and enhanced apoptotic cells via caspase activation in ex vivo peripheral blood monocytes from asymptomatic HTLV‐1 carriers (ACs) or via caspase‐independent cell death in acute‐type ATL, which has a poor prognosis. Telmisartan also induced significant growth inhibition and apoptosis in leukemia cell lines via caspase activation, whereas other angiotensin II receptor blockers did not induce cell death. Interestingly, telmisartan increased the LC3‐II‐enriched protein fraction, indicating autophagosome accumulation and autophagy. Thus, telmisartan simultaneously caused caspase activation and autophagy. A hypertension medication with antiproliferation effects on primary and leukemia cells is intriguing. Patients with an early diagnosis of ATL are generally monitored until the disease progresses; thus, suppression of progression from AC and indolent ATL to acute ATL is important. Our results suggest that telmisartan is highly effective against primary cells and leukemia cell lines in caspase‐dependent and ‐independent manners, and its clinical use may suppress acute transformation and improve prognosis of patients with this mortal disease. This is the first report demonstrating a cell growth‐inhibitory effect of telmisartan in fresh peripheral blood mononuclear cells from leukemia patients. Abstract : Telmisartan reduced cell viability and enhanced apoptotic cells via caspase activation in ex vivo peripheral blood monocytes from asymptomatic HTLV‐1 carriers or via caspase‐independent cell death in acute type ATL. Telmisartan also induced significant growth inhibition and apoptosis in leukemia cell lines via caspase activation. Interestingly, telmisartan increased the LC3‐II‐enriched protein fraction, indicating autophagosome accumulation and autophagy.