title: 3,3',4', 5'-Tetramethoxychalcone inhibits human oral cancer cell proliferation and migration via p53-mediated mitochondrial-dependent apoptosis.
abstract: OBJECTIVE
  The current study aimed to identify an attractive target against human oral squamous cell carcinoma (OSCC).
  
  
  METHODS
  The effect of 3,3',4',5'-tetramethoxychalcone (TMC) on OSCC cell proliferation, cell-cycle phase distribution, expression of markers of cell apoptosis, and cell migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, western blot, and transwell migration assay, respectively.
  
  
  RESULTS
  Experimental results revealed that TMC inhibited the OSCC cell proliferation (fifty percent inhibitory concentrations range=1.0-4.5 μM) by inducing G2/M phase arrest of the cell cycle. TMC caused DNA double-strand breaks, and enhanced expression of caspase-3 and -9, poly (ADP-ribose) polymerase, cytochrome c, calpain-1 and -2, phosphorylation of histone H2AX, phosphorylation of checkpoint kinases 2, p53, BCL2-antagonist/killer and BCL2-associated × protein, while reducing the mitochondrial membrane potential, and expression of B-cell lymphoma-2. In addition, TMC reduced the migration potential of OSCC cells by attenuating the C-C chemokine ligand 5/C-C chemokine receptor type 5 axis.
  
  
  CONCLUSIONS
  These data indicate that TMC may be considered an interesting target for further development of chemotherapeutic agents against oral cancer.
authors.affiliation: Chaoyang University of Technology, Taichung, Taiwan, R.O.C. Tel: +886 423323000 ext. 4471, ymtzeng@cyut.edu.tw.
authors.forename: Cheng-Kuo
authors.initials: CK
authors.lastname: Lai
authors.forename: Yerra Koteswara
authors.initials: YK
authors.lastname: Rao
authors.forename: Kai-Ruei
authors.initials: KR
authors.lastname: Chang
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Lin
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Su
authors.forename: Chia-Shuo
authors.initials: CS
authors.lastname: Chang
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
authors.forename: Yew-Min
authors.initials: YM
authors.lastname: Tzeng
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D018946:Chemokine CCL5 / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D019713:Receptors, CCR5 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D018946:Chemokine CCL5; D019713:Receptors, CCR5; D016159:Tumor Suppressor Protein p53; D002599:Chalcone
keywords: 3,3’,4’,5’-tetramethoxychalcone; CCL5/CCR5 axis; DNA double-strand breaks; Oral cancer; apoptosis; cell migration; cell proliferation