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Kozako T, Soeda S, Yoshimitsu M, et al. Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells. FEBS Open Bio. 2016;6(5):442-60doi: 10.1002/2211-5463.12055.
Kozako, T., Soeda, S., Yoshimitsu, M., Arima, N., Kuroki, A., Hirata, S., Tanaka, H., Imakyure, O., Tone, N., Honda, S., & Soeda, S. (2016). Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells. FEBS open bio, 6(5), 442-60. https://doi.org/10.1002/2211-5463.12055
Kozako, Tomohiro, et al. "Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells." FEBS open bio vol. 6,5 (2016): 442-60. doi: https://doi.org/10.1002/2211-5463.12055
Kozako T, Soeda S, Yoshimitsu M, Arima N, Kuroki A, Hirata S, Tanaka H, Imakyure O, Tone N, Honda S, Soeda S. Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells. FEBS Open Bio. 2016 Apr 13;6(5):442-60. doi: 10.1002/2211-5463.12055. eCollection 2016 May. PMID: 27419050; PMCID: PMC4856423.
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FEBS Open Bio. 2016 Apr 13;6(5):442-60. doi: 10.1002/2211-5463.12055. eCollection 2016 May.

Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells.

FEBS open bio

Tomohiro Kozako, Shuhei Soeda, Makoto Yoshimitsu, Naomichi Arima, Ayako Kuroki, Shinya Hirata, Hiroaki Tanaka, Osamu Imakyure, Nanako Tone, Shin-Ichiro Honda, Shinji Soeda

Affiliations

  1. Department of Biochemistry Faculty of Pharmaceutical Sciences Fukuoka University Japan.
  2. Department of Hematology and Immunology Kagoshima University Hospital Japan; Division of Hematology and Immunology School of Medical and Dental Sciences Center for Chronic Viral Diseases Graduate Kagoshima University Japan.
  3. Division of Hematology and Immunology School of Medical and Dental Sciences Center for Chronic Viral Diseases Graduate Kagoshima University Japan.
  4. Department of Rheumatology and Clinical Immunology Kumamoto University Hospital Japan.
  5. Faculty of Sports and Health Science Fukuoka University Japan.
  6. Department of Pharmaceutical Care and Health Sciences Faculty of Pharmaceutical Sciences Fukuoka University Japan.

PMID: 27419050 PMCID: PMC4856423 DOI: 10.1002/2211-5463.12055

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.

Keywords: adult T‐cell leukemia/lymphoma; apoptosis; autophagy; drug repositioning; human T‐cell leukemia virus‐1; telmisartan

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