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SIRT1 is a histone deacetylase involved in cell cycle and apoptosis. We previously showed the high expression of SIRT1 protein in peripheral blood mononuclear cells from patients with ATL. There have been many reports that SIRT1 inhibitors show tumor\u2010suppressive effects. On the other hand, SIRT1 activator SRT1720 induces the cell death of multiple myeloma and breast cancer cells. However, the effect of SRT1720 on ATL is unknown. This study aimed to evaluate the effect of SRT1720 on cell death in leukemic cell lines\n                    <jats:italic>in\u2009vitro<\/jats:italic>\n                    and freshly isolated ATL cells\n                    <jats:italic>ex\u2009vivo<\/jats:italic>\n                    and in an ATL\n                    <jats:italic>in\u2009vivo<\/jats:italic>\n                    mouse model. SRT1720 reduced cell viability\n                    <jats:italic>in\u2009vitro<\/jats:italic>\n                    and\n                    <jats:italic>ex\u2009vivo<\/jats:italic>\n                    . Additionally, SRT1720 increased the number of apoptotic cells, as shown by annexin V positive cells, cleaved poly (ADP\u2010ribose) polymerase 1, cleaved caspase\u20103, and fragmented DNA. SRT1720 also induced mitochondrial outer membrane permeabilization with the generation of mitochondrial reactive oxygen species and autophagy. However,\n                    <jats:italic>SIRT1<\/jats:italic>\n                    knockdown did not attenuate SRT1720\u2010induced cell death in leukemic cell lines. Finally, SRT1720 treatment decreased the growth of human ATL tumor xenografts in immunodeficient mice. Our study shows that while SRT1720 does not target SIRT1, it induces cell death in ATL cells via apoptosis and autophagy and has antitumor activity.\n                  <\/jats:p>","DOI":"10.1111\/febs.16353","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T23:43:26Z","timestamp":1642117406000},"page":"3477-3488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["SRT1720 induces SIRT1\u2010independent cell death in adult T\u2010cell leukemia\/lymphoma"],"prefix":"10.1111","volume":"289","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9439-4335","authenticated-orcid":false,"given":"Tomohiro","family":"Kozako","sequence":"first","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmaceutical Sciences Fukuoka University  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