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We previously reported that cyclo(\u2010Pro\u2010Tyr) (CPT), a dipeptide from marine sponge <jats:italic>Callyspongia fistularis<\/jats:italic> associated <jats:italic>Bacillus pumilus<\/jats:italic> AMK1 bacteria for its anti\u2010proliferative activity through down regulating PI3K signaling and inducing mitochondrial mediated apoptosis in HepG2 cells. Further we emphasize to study the role of CPT against hepatocellular carcinoma (HCC) induced by N\u2010diethylnitrosamine (DEN) in male swiss albino mice in vivo. In this study, HCC was induced by the administration of DEN (75\u2009mg\/kg b.wt) dissolved in saline once\/week for 3\u2009weeks, then 100\u2009mg\/kg b.wt for another successive 3\u2009weeks and observed for 18\u2009weeks. CPT (100\u2009mg\/kg b.wt) treatment was started after 14\u2009weeks of DEN induction. The obtained results demonstrated that CPT altered DEN induced oxidative stress by decreasing serum SGOT and SGPT followed increment in the antioxidants such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. This was accompanied by decreased accumulation of glycoconjugates and argyophilic nucleolar organizing regions in the treatment groups. Further, CPT significantly reduced the levels of phospho\u2010PI3Kinase p85 and phospho\u2010AKT and upregulation of PTEN compared with DEN induced group. Besides this, decreased expression of Bcl\u20102 and increased expression of Bax, Caspase 3, and p53 was observed in CPT treated mice. Therefore, the anticancer mechanism of CPT against DEN induced HCC may be associated with the regulation of the PI3K\/AKT signaling pathway, which ultimately stimulates apoptosis.<\/jats:p>","DOI":"10.1002\/tox.23395","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T12:42:37Z","timestamp":1635856957000},"page":"256-269","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Potential anticancer effects of cyclo(\u2010Pro\u2010Tyr) against N\u2010diethyl nitrosamine induced hepatocellular carcinoma in mouse through PI3K\/AKT signaling"],"prefix":"10.1002","volume":"37","author":[{"given":"Gayathri","family":"Karanam","sequence":"first","affiliation":[{"name":"Cancer Biology Lab, Centre for Molecular and Nanomedical Sciences Sathyabama Institute of Science and Technology  Chennai Tamil Nadu 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