{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:23:42Z","timestamp":1785435822422,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research"},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["Next Generation EU_2022W97H54_003-CUP J53D23001200006"],"award-info":[{"award-number":["Next Generation EU_2022W97H54_003-CUP J53D23001200006"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"award":["Next Generation EU_2022W97H54_003-CUP J53D23001200006"],"award-info":[{"award-number":["Next Generation EU_2022W97H54_003-CUP J53D23001200006"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human T-Lymphotropic virus type 1 (HTLV-1) lifelong infects at least 5\u201310 million people worldwide, a minority of whom develop severe lethal diseases including adult T-cell Leukemia\/lymphoma and HTLV-1-associated myelopathy or tropical spastic paraparesis. Currently, no vaccines or curative therapies to fight HTLV-1 infection or diseases are available. Recently we found that a tributyltin molecule, Bu3SnOCOCF3 (TBT), which is more potent than cisplatin in inducing cytotoxic effects towards a panel of cell lines including high-tumorigenic cells, also exerted potent cytotoxic effects even towards HTLV-1-infected cell lines, mimicking different states of virus-driven transformation. The type of cell death involved was elusive. In the present study, the effects of TBT on virological and cell death parameters were investigated in HTLV-1-infected immortalized lymphocytes generated by in vitro infection and rendered with or without progressive independence from interleukin-2 as a growth factor. Molecular studies demonstrated that TBT affected HTLV-1 viral gene expression, especially HBZ. TBT confirmed its high cytotoxic potential on the HTLV-1-infected cell lines assayed, especially towards the IL-2-independent HTLV-1-infected cells. Investigation of mechanisms involved in cell death induced by TBT in HTLV-1-infected cells confirmed that caspase 3 and 8 activation, as well as apoptotic response, were relevant. In addition, pyroptosis as well as other unspecifed forms of lytic death presumably contribute to cell death induced by TBT in HTLV-1-infected cells, while a concomitant activation of an autophagic response by this compound seems to mitigate it. Overall, these experimental results outline a particular profile of TBT-induced cell death in HTLV-1-infected cells that is useful for future studies aimed at verifying the real potential of tin-based compounds to contrast diseases caused by HTLV-1.<\/jats:p>","DOI":"10.3390\/ijms27146165","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T11:43:34Z","timestamp":1783683814000},"page":"6165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the Mechanisms Underlying Cell Death Induction by a Tributyltin Molecule in HTLV-1-Infected Cells Dependent or Not on IL-2 as a Growth Factor"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4192-7497","authenticated-orcid":false,"given":"Valeria","family":"Stefanizzi","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8359-3178","authenticated-orcid":false,"given":"Evariste","family":"Molimbou","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Balestrieri","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4784-4297","authenticated-orcid":false,"given":"Antonella","family":"Minutolo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6005-5941","authenticated-orcid":false,"given":"Franca M.","family":"Cordero","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry \u201cUgo Schiff\u201d, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1028-3203","authenticated-orcid":false,"given":"Sandro","family":"Grelli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0338-6450","authenticated-orcid":false,"given":"Antonio","family":"Mastino","sequence":"additional","affiliation":[{"name":"The Institute of Translational Pharmacology, Consiglio Nazionale delle Ricerche (C.N.R.), 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6058-1092","authenticated-orcid":false,"given":"Claudia","family":"Matteucci","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0878-1799","authenticated-orcid":false,"given":"Beatrice","family":"Macchi","sequence":"additional","affiliation":[{"name":"Department of Chemical Science and Technology, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7898-583X","authenticated-orcid":false,"given":"Francesca","family":"Marino-Merlo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","article-title":"Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma","volume":"77","author":"Poiesz","year":"1980","journal-title":"Proc. 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