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The present study was designed to purify the molecules from <jats:italic>Thymus linearis<\/jats:italic> and elucidate their antiproliferative activity. The compounds were isolated from the active methanolic extract of <jats:italic>Thymus linearis<\/jats:italic> through column chromatography and characterized by various spectroscopic techniques. Antiproliferative activity of isolated compounds was evaluated using MTT assay on cancer and normal cell lines. Mechanism of cell death was elucidated using flow cytometric, microscopic, and Western blot analysis. Four compounds, <jats:italic>Sitosterol<\/jats:italic>, Chrysin, 3\u03b2\u2010hydroxylup\u201012\u2010en\u201028\u2010oic acid (3BH), and \u03b2\u2010<jats:italic>Sitosterol glycoside<\/jats:italic>, were isolated. Among these, 3BH was most potent antiproliferative agent across all cell lines under study, HCT\u2010116 being the most affected one. 3BH was demonstrated to downregulate PI3Ksubunits (p110\u03b1 and p85\u03b1), downstream pAktSer<jats:sup>473<\/jats:sup> and prompted G<jats:sub>1<\/jats:sub> phase cell cycle arrest. The cell cycle CDK inhibitor p27 and p21 were upregulated with simultaneous downregulation of cyclin D1 and cyclin E in HCT\u2010116 cells. This was accompanied by apoptosis, as depicted by decrease in Bcl\u20102\/Bax ratio, with increase in active caspases\u20103 and caspase\u20109, cleavage of PARP\u20101, the generation of reactive oxygen species (ROS), and the loss of mitochondrial membrane potential. The findings established that 3BH induced cell death in HCT\u2010116 cells by modulating PI3K\/Akt signaling axis, impeding cell cycle, and instigating apoptosis.<\/jats:p>","DOI":"10.1111\/cbdd.13957","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T08:45:32Z","timestamp":1632473132000},"page":"162-178","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The modulation of PI3K\/Akt pathway by 3\u03b2 hydroxylup\u201012\u2010en\u201028\u2010oic acid isolated from <i>Thymus linearis<\/i> induces cell death in HCT\u2010116 cells"],"prefix":"10.1111","volume":"99","author":[{"given":"Rohina","family":"Bashir","sequence":"first","affiliation":[{"name":"Department of Biochemistry University of Kashmir  Hazratbal Srinagar India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ovais","family":"Ahmad Zargar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Kashmir  Hazratbal Srinagar India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abid","family":"Hamid Dar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Central University of Kashmir  Ganderbal India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nalli","family":"Yedukondalu","sequence":"additional","affiliation":[{"name":"CSIR\u2010Indian Institute of Integrative Medicine  Jammu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qazi","family":"Parvaiz","sequence":"additional","affiliation":[{"name":"Microbial Biotechnology Division CSIR\u2010 Indian Institute of Integrative Medicine Sanat Nagar Srinagar  India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabia","family":"Hamid","sequence":"additional","affiliation":[{"name":"Department of Nanotechnology University of Kashmir  Hazratbal Srinagar India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2018.07.010"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476\u20104598\u20106\u201024"},{"key":"e_1_2_8_4_1","first-page":"1562","article-title":"Natural products as treatment against cancer: A historical and current vision","volume":"4","author":"Amaral R. 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