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Molecular techniques have been used to investigate the mechanisms of action and the beneficial therapeutic effects of halofuginone (HF) in several cancers but not malignant mesotheliomas. In this study, the antiproliferative and apoptotic effects of HF were investigated through its ability to deregulate EGFR downstream signalling cascade proteins in the pathologically aggressive malignant mesothelioma and non\u2010small\u2010cell lung cancer cells. We showed that administration of HF at nanomolar concentrations induced a dose\u2010dependent reduction in the viability of cancer cells, made cell cycle arrest, inhibited proliferation of cancer cells via STAT3 and ERK1\/2 pathways and triggered the apoptotic cascade via p38MAPK. We demonstrated that the apoptotic cell death mechanism was mediated by enhanced activation of caspase\u20103 and concomitant PARP cleavage, downregulation of Bcl\u20102 and upregulation of Bax in both malignant mesothelioma and lung cancer cells. In particular, we demonstrated that cancer cells were more sensitive to HF treatment than normal mesothelial cells. Taken together, this study suggests that HF exerts its anticancer effects in lung\u2010derived cancers by targeting signal transduction pathways mainly through deregulation of ERK1\/2, STAT3 and p38MAPK to reduce cancer cell viability, induce cell cycle arrest and apoptotic cell death. Thus, HF might be considered as a potential agent against malignant mesothelioma and\/or lung cancer cells.<\/jats:p>","DOI":"10.1002\/cbin.11399","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T12:51:04Z","timestamp":1590065464000},"page":"1934-1944","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Anticarcinogenic effects of halofuginone on lung\u2010derived cancer cells"],"prefix":"10.1002","volume":"44","author":[{"given":"Asuman","family":"Demiroglu\u2010Zergeroglu","sequence":"first","affiliation":[{"name":"Department of Molecular Biology &amp; Genetics, Faculty of Science Gebze Technical University  Gebze Kocaeli Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulseren","family":"Turhal","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology &amp; Genetics, Faculty of Science Gebze Technical University  Gebze Kocaeli Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Halime","family":"Topal","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology &amp; Genetics, Faculty of Science Gebze Technical University  Gebze Kocaeli Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hurmuz","family":"Ceylan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology &amp; Genetics, Faculty of Science Gebze Technical University  Gebze Kocaeli Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fadime","family":"Donbaloglu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology &amp; Genetics, Faculty of Science Gebze Technical University  Gebze Kocaeli Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kivilcim","family":"Karadeniz Cerit","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, School of Medicine Marmara University  Pendik Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald R.","family":"Odongo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology &amp; Genetics, Faculty of Science Gebze Technical University  Gebze Kocaeli Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.03520"},{"issue":"1","key":"e_1_2_9_3_1","first-page":"13","article-title":"Expression of activated and latent signal transducer and activator of transcription 3 in 303 non\u2010small cell lung carcinomas and 44 malignant mesotheliomas: Expression of activated and latent signal transducer and activator of transcription 3 in 303 non\u2010small cell lung carcinomas and 44 malignant mesotheliomas: Possible role for chemotherapeutic intervention","volume":"132","author":"Achcar R. 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