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In the present study, we have reported the protective effect of a natural compound, thymoquinone (TQ) against benzo(<jats:italic>a<\/jats:italic>)pyrene (B(a)P)\u2010induced lung carcinogenesis in Swiss albino mice. B(a)P (50\u2009mg\/kg body weight) was administered twice weekly for four successive weeks and left until 20 weeks to induce lung cancer in mice. TQ (20\u2009mg\/kg body weight) was given orally as a pretreatment and posttreatment drug to determine its chemopreventive and therapeutic effects. B(a)P\u2010induced lung cancer\u2010bearing animals displayed cachexia\u2010like symptoms along with an abnormal increase in lung weight and the activities of marker enzymes adenosine deaminase, aryl hydrocarbon hydroxylase, gamma\u2010glutamyl transpeptidase, 5\u2032\u2010nucleotidase and lactate dehydrogenase; tumor marker carcinoembryonic antigen levels. Furthermore, B(a)P\u2010induced animals showed elevated levels of lipid peroxides with subsequent depletion in the antioxidant status and histological aberrations. These anomalies were accompanied by increased expressions of proliferating cell nuclear antigen and cyclin D1 in the lung sections derived from B(a)P\u2010induced animals. On TQ treatment, all the above alterations were returned to near normalcy. Furthermore, TQ administration in B(a)P\u2010induced animals downregulated phosphatidylinositol 3\u2010kinase\/protein kinase B signaling pathway and induced apoptosis as evidenced by a decrease in cytochrome c, proapoptotic Bax, caspase\u20103, and p53 with a parallel increase in antiapoptotic Bcl\u20102. Our present results demonstrate the potential effectiveness of TQ as an antioxidant, antiproliferative, and apoptotic agent against B(a)P\u2010induced experimental lung tumorigenesis.<\/jats:p>","DOI":"10.1002\/jbt.23230","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T01:54:14Z","timestamp":1664848454000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Antioxidant, antiproliferative, and apoptotic activity of thymoquinone against benzo(<i>a<\/i>)pyrene\u2010induced experimental lung cancer"],"prefix":"10.1002","volume":"37","author":[{"given":"Gajendran","family":"Nithya","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Dr. ALM PGIBMS, University of Madras Taramani Campus Chennai Tamil Nadu 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