title: Cantharidin inhibits cell proliferation and promotes apoptosis in tongue squamous cell carcinoma through suppression of miR-214 and regulation of p53 and Bcl-2/Bax.
abstract: Cantharidin, a type of terpenoid, is a chemical compount secreted by the blister beetle or Mylabris phelarata pallas of the Meloidae family. Cantharidin is known to have good antitumor activity. The present study aimed to investigate the anticancer effect of cantharidin and its possible underlying mechanism using tongue squamous cell carcinoma (TSCC) TCA8113 cells. TCA8113 cells were treated with various concentrations of cantharidin, and the cell viability and cytotoxicity were assessed using MTT and LDH assays, respectively. Flow cytometry was conducted to examine cell apoptosis and colorimetric protease assay was performed to analyze caspase-9/3 activities in TCA8113 cells. qPCR and western blot analysis were used to investigate microRNA-214 (miR-214) expression, as well as the expression of p53, Bcl-2 and Bax proteins in TCA8113 cells. miR-214 and anti-miR-214 were transfected with mimics to examine whether miR-214 expression regulated the anticancer effect of cantharidin on TCA8113 cells and p53, Bcl-2 and Bax protein expression. The anticancer effect of cantharidin significantly inhibited cell proliferation and increased cytotoxicity of TSCC Tca8113 cells in a dose- and time-dependent manner. In addition, cantharidin induced cell apoptosis and activated caspase-9/3 activities of TSCC Tca8113 cells. Cantharidin markedly weakened miR-214 expression level, activated p53 protein expression, and suppressed the Bcl-2/Bax signaling pathway in Tca8113 cells. Downregulation of miR-214 increased p53 protein expression and decreased the Bcl-2/Bax signaling pathway of TSCC Tca8113 cells. However, the overexpression of miR-214 reduced the anticancer effect of cantharidin on the proliferation and apoptosis of TSCC Tca8113 cells, inhibited p53 protein expression, and increased the Bcl-2/Bax signaling pathway. The results suggested that cantharidin is a potential anticancer drug that can be used to regulate the proliferation and apoptosis of human TSCC Tca8113 cells. Additionally, its mechanism may partially be associated with the downregulation of miR-214, upregulation of p53 protein expression and suppression of the Bcl-2/Bax signaling pathway.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Plastic and Burn Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Guang
authors.initials: G
authors.lastname: Zeng
authors.affiliation: Hospital of Chongming Air Force Field, Shanghai 202150, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, The 88th Hospital of PLA, Tai'an, Shandong 271000, P.R. China.
authors.forename: Zizhong
authors.initials: Z
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D002193:Cantharidin / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D002193:Cantharidin