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This study aimed to analyze whether chronic <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content> 30\u2013100\u00a0K stimulations lead to higher stress resistance and autophagic activity in oral cells, and whether the resulting autophagic status in stimulated cells correlates with stress resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Malignant cells from the mouth oral epidermoid carcinoma Meng\u20101 (<jats:styled-content style=\"fixed-case\">OECM<\/jats:styled-content>\u20101) and blood (Jurkat <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>) origins were stimulated with non\u2010cytotoxic <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content> 30\u2013100\u00a0K for 3\u00a0months. Sensitivity to anticancer drugs of and autophagy status in stimulated cells, analyzed respectively by <jats:styled-content style=\"fixed-case\">XTT<\/jats:styled-content> assay and calculating microtubule\u2010associated protein 1 light chain 3\u2010II LC3\u2010II\/\u03b2\u2010actin ratios from <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>estern blot, were compared to non\u2010treated cells. Autophagy inhibitors, 3\u2010methyladenine (3\u2010<jats:styled-content style=\"fixed-case\">MA<\/jats:styled-content>) and chloroquine (<jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>), were used to assess whether autophagy inhibition interferes the altered chemoresistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Areca nut extract\u2010stimulated (<jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content>\u2010s) and <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content> 30\u2013100\u00a0K\u2010stimulated (30\u2013100\u00a0K\u2010s) <jats:styled-content style=\"fixed-case\">OECM<\/jats:styled-content>\u20101 and Jurkat <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells generally exhibited higher cisplatin and 5\u2010fluorouracil (5\u2010<jats:styled-content style=\"fixed-case\">FU<\/jats:styled-content>) resistances, compared to non\u2010stimulated cells. Most stimulated cells expressed significantly higher levels of LC3\u2010II and Atg4B proteins. Interestingly, these cells also showed stronger tolerances against hypoxia environment and expressed higher LC3\u2010II levels under glucose\u2010deprived and hypoxia conditions. Finally, both 3\u2010<jats:styled-content style=\"fixed-case\">MA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content> alleviated, albeit to different degrees, the increased chemoresistance in <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content>\u2010s and\/or 30\u2013100\u00a0K\u2010s cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Chronic stimulations of <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content> 30\u2013100\u00a0K may increase tolerance of oral cancer and leukemia <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells to anticancer drugs, as well as to glucose deprivation and hypoxia conditions, and cause an elevation of autophagy activity responsible for increased drug resistance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12102","type":"journal-article","created":{"date-parts":[[2013,6,25]],"date-time":"2013-06-25T03:47:19Z","timestamp":1372132039000},"page":"91-96","source":"Crossref","is-referenced-by-count":21,"title":["Long\u2010term stimulation of areca nut components results in increased chemoresistance through elevated autophagic activity"],"prefix":"10.1111","volume":"43","author":[{"given":"Ching\u2010Yu","family":"Yen","sequence":"first","affiliation":[{"name":"Department of Dentistry Taipei Medical University Taipei Taiwan"},{"name":"Department of Dentistry National Defense Medical Center Taipei Taiwan"},{"name":"Oral and Maxillofacial Surgery Section Chi Mei Medical Center Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Fan","family":"Chiang","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Section Chi Mei Hospital Liouying Taiwan"},{"name":"School of Dentistry 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