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Regimens that include platinum-based drugs provide high response rates in different B cell lymphomas, high-risk chronic lymphocytic leukemia (CLL), and devastating complication of CLL, Richter\u2019s syndrome. The aim of this study was to explore the potential antitumor activity of previously synthetized platinum(IV) complex with alkyl derivatives of thyosalicilc acid, PtCl2(S-pr-thiosal)2, toward murine BCL1 cells and to delineate possible mechanisms of action. The PtCl2(S-pr-thiosal)2 reduced the viability of BCL1 cells in vitro but also reduced the growth of metastases in the leukemia lymphoma model in BALB\/c mice. PtCl2(S-pr-thiosal)2 induced apoptosis, inhibited proliferation of BCL1 cells, and induced cell cycle disturbance. Treatment of BCL1 cells with PtCl2(S-pr-thiosal)2 inhibited expression of cyclin D3 and cyclin E and enhanced expression of cyclin-dependent kinase inhibitors p16, p21, and p27 resulting in cell cycle arrest in the G1 phase, reduced the percentage of BCL1 cells in the S phase, and decreased expression of Ki-67. PtCl2(S-pr-thiosal)2 treatment reduced expression of phosphorylated STAT3 and downstream-regulated molecules associated with cancer stemness and proliferation, NANOG, cyclin D3, and c-Myc, and expression of phosphorylated NF\u03baB in vitro and in vivo. In conclusion, PtCl2(S-pr-thiosal)2 reduces STAT3 and NF\u03baB phosphorylation resulting in inhibition of BCL1 cell proliferation and the triggering of apoptotic cell death.<\/jats:p>","DOI":"10.3390\/ijms23158161","type":"journal-article","created":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T22:49:02Z","timestamp":1658702942000},"page":"8161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Pt(S-pr-thiosal)2 and BCL1 Leukemia Lymphoma: Antitumor Activity In Vitro and In Vivo"],"prefix":"10.3390","volume":"23","author":[{"given":"Zana Besser","family":"Silconi","sequence":"first","affiliation":[{"name":"Department of Cytology, Pula General Hospital, 52100 Pula, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4264-845X","authenticated-orcid":false,"given":"Vesna","family":"Rosic","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasa","family":"Benazic","sequence":"additional","affiliation":[{"name":"Department of Transfusiology, Pula General Hospital, 52100 Pula, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordana","family":"Radosavljevic","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7177-4666","authenticated-orcid":false,"given":"Marina","family":"Mijajlovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Pantic","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoran R.","family":"Ratkovic","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordana","family":"Radic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Arsenijevic","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Milovanovic","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nebojsa","family":"Arsenijevic","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Milovanovic","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"},{"name":"Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6524","DOI":"10.1038\/sj.onc.1207843","article-title":"The epidemiology of non-Hodgkin\u2019s lymphoma","volume":"23","author":"Fisher","year":"2004","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12938-021-00973-6","article-title":"The global burden and attributable risk factors of chronic lymphocytic leukemia in 204 countries and territories from 1990 to 2019: Analysis based on the global burden of disease study 2019","volume":"21","author":"Yao","year":"2022","journal-title":"Biomed. 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