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Hepatocellular carcinoma (HCC) has few treatment options, and unfortunately, the prognosis is poor. Thus, the development of novel therapeutic drugs is urgent. The present study aimed at evaluating the antitumor mechanism of selenylated IP\u00a0against HepG2\u00a0cells and in vivo. The selenylated IP named <jats:bold>IP\u2010Se\u201006<\/jats:bold> (3\u2010((2\u2010methoxyphenyl)selanyl)\u20107\u2010methyl\u20102\u2010phenylimidazol[1,2\u2010<jats:italic>a<\/jats:italic>]pyridine) showed high cytotoxicity against HepG2 cells (half\u2010maximal\u00a0inhibitory concentration [IC<jats:sub>50<\/jats:sub>]\u2009=\u20090.03\u2009\u00b5M) and selectivity for this tumor cell line. At nontoxic concentration, <jats:bold>IP\u2010Se\u201006<\/jats:bold>\u00a0decreased the protein levels of Bcl\u2010xL and increased the levels of p53, leading to inhibition of cell proliferation and apoptosis. This compound decreased the level of extracellular signal\u2010regulated kinase 1\/2 protein and changed the levels of proteins involved in the drive of the cell cycle, tumor growth, and survival (cyclin B1, cyclin\u2010dependent kinase 2). In addition, <jats:bold>IP\u2010Se\u201006<\/jats:bold> decreased the number of cells in the S phase. In addition, <jats:bold>IP\u2010Se\u201006<\/jats:bold> led to increased generation of reactive oxygen species, changed antioxidant defenses, and caused DNA fragmentation. Finally, <jats:bold>IP\u2010Se\u201006<\/jats:bold> significantly inhibited the growth of Ehrlich ascites tumors in mice, increased survival time, and inhibited angiogenesis. Therefore, <jats:bold>IP\u2010Se\u201006<\/jats:bold> may be an important compound regarding the development of a therapeutic drug for HCC treatment.<\/jats:p>","DOI":"10.1002\/jbt.22663","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T14:33:04Z","timestamp":1604068384000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Apoptosis oxidative damage\u2010mediated and antiproliferative effect of selenylated imidazo[1,2\u2010<i>a<\/i>]pyridines on hepatocellular carcinoma HepG2 cells and in vivo"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9916-6814","authenticated-orcid":false,"given":"Daniela Coelho","family":"dos Santos","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Laborat\u00f3rio de Bioqu\u00edmica Experimental (LABIOEX) Universidade Federal de Santa Catarina (UFSC)  Florian\u00f3polis Santa Catarina 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