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Histologically, about 85\u201390% of oral cavity cancers are of the type squamous cells carcinomas (SCCs). The incidence of oral tongue SCC is higher in the tongue than any other anatomic area of the oral cavity. Here, we investigated the therapeutic effects and molecular mechanisms of docetaxel, which is a paclitaxel antitumor agent, on the cell growth of a human tongue SCC-derived SAS cell line. The results showed that docetaxel (10\u2013300 nM) induced cytotoxicity and caspase-3 activity in SAS cells. Moreover, docetaxel (100 nM) promoted the expression of apoptosis-related signaling molecules, including the cleavages of caspase-3, caspase-7, and poly (ADP-ribose) polymerase (PARP). In mitochondria, docetaxel (100 nM) decreased the mitochondrial membrane potential (MMP) and Bcl-2 mRNA and protein expression and increased cytosolic cytochrome c protein expression and Bax mRNA and protein expression. In terms of mitogen-activated protein kinase (MAPK) and adenosine monophosphate-activated protein kinase (AMPK) signaling, docetaxel increased the expression of phosphorylated (p)-extracellular signal-regulated kinase (ERK), p-c-Jun N-terminal kinase (JNK), and p-AMPK\u03b1 protein expression but not p-p38 protein expression. Moreover, the increase in caspase-3\/-7 activity and Bax protein expression and decreased Bcl-2 protein expression and MMP depolarization observed in docetaxel-treated SAS cells could be reversed by treatment with either SP600125 (a JNK inhibitor), PD98059 (an MEK1\/2 (mitogen-activated protein kinase kinase 1\/2) inhibitor), or compound c (an AMPK inhibitor). The docetaxel-induced increases in p-JNK, p-ERK, and p-AMPK\u03b1 protein expression could also be reversed by treatment with either SP600125, PD98059, or compound c. These results indicate that docetaxel induces human tongue SCC cell apoptosis via interdependent MAPK-JNK, MAPK-ERK1\/2, and AMPK\u03b1 signaling pathways. Our results show that docetaxel could possibly exert a potent pharmacological effect on human oral tongue SCC cell growth.<\/jats:p>","DOI":"10.3390\/ijms232213857","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T19:16:23Z","timestamp":1668107783000},"page":"13857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Involvement of AMPK\u03b1 and MAPK-ERK\/-JNK Signals in Docetaxel-Induced Human Tongue Squamous Cell Carcinoma Cell Apoptosis"],"prefix":"10.3390","volume":"23","author":[{"given":"Chin-Chuan","family":"Su","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua County, Changhua County 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jhe-Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai-Yao","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Emergency, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7240-8465","authenticated-orcid":false,"given":"Cheng-Tien","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, China Medical University, Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-1197","authenticated-orcid":false,"given":"Shing-Hwa","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai-Chih","family":"Chang","sequence":"additional","affiliation":[{"name":"Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3868-085X","authenticated-orcid":false,"given":"Jui-Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 330, Taiwan"},{"name":"Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan-I","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Emergency, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 427, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0505-1109","authenticated-orcid":false,"given":"Kai-Min","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.soc.2015.03.006","article-title":"Cancer of the oral cavity","volume":"24","author":"Montero","year":"2015","journal-title":"Surg. 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