{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T06:02:47Z","timestamp":1776578567477,"version":"3.51.2"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The therapeutic goal of cancer treatment is now geared towards triggering tumour\u2010selective cell death with autophagic cell death being required for the chemotherapy of apoptosis\u2010resistant cancer. In this study, Carnosic acid (CA), a polyphenolic diterpene isolated from Rosemary (<jats:italic>Rosemarinus officinalis<\/jats:italic>), significantly induced autophagic cell death in HepG2 cells. Ca treatment caused the formation of autophagic vacuoles produced an increasing ratio of LC3\u2010II to LC3\u2010I in a time\u2010 and dose\u2010dependent manner but had no effect on the levels of autophagy\u2010related protein ATG6 and ATG13 expression. Autophagy inhibitors, 3\u2010methyladenine (3\u2010MA), chloroquine and bafilomycin A1, or ATG genes silencing in HepG2 cells significantly inhibited CA\u2010induced autophagic cell death. The CA treatment decreased the levels of phosphorylated Akt and mTOR without any effects on PI3K or PTEN. Most importantly, overexpression of Akt and knockdown of PTEN attenuated autophagy induction in CA\u2010treated cells. Taken together, our results indicated that CA induced autophagic cell death through inhibition of the Akt\/mTOR pathway in human hepatoma cells. These findings suggest that CA has a great potential for the treatment of hepatoma via autophagic induction. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3049","type":"journal-article","created":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T08:19:18Z","timestamp":1409559558000},"page":"485-492","source":"Crossref","is-referenced-by-count":48,"title":["Carnosic acid induces autophagic cell death through inhibition of the Akt\/mTOR pathway in human hepatoma cells"],"prefix":"10.1002","volume":"35","author":[{"given":"Qilong","family":"Gao","sequence":"first","affiliation":[{"name":"Department of integrated traditional Chinese and western medicine Affiliated cancer hospital of Zhengzhou University  Zhengzhou Henan 450008 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaimin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of integrated traditional Chinese and western medicine Affiliated cancer hospital of Zhengzhou University  Zhengzhou Henan 450008 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