title: Curcumin inhibits AP-2γ-induced apoptosis in the human malignant testicular germ cells in vitro.
abstract: OBJECTIVE
  To investigate the effects of curcumin on proliferation and apoptosis in testicular cancer cells in vitro and to investigate its molecular mechanisms of action.
  
  
  METHODS
  NTera-2 human malignant testicular germ cell line and F9 mouse teratocarcinoma stem cell line were used. The anti-proliferative effect was examined using MTT and colony formation assays. Hoechst 33258 staining, TUNEL and Annexin V-FITC/PI staining assays were used to analyze cell apoptosis. Protein expression was examined with Western blot analysis and immunocytochemical staining.
  
  
  RESULTS
  Curcumin (5, 10 and 15 μmol/L) inhibited the viability of NTera-2 cells in dose- and time-dependent manners. Curcumin significantly inhibited the colony formation in both NTera-2 and F9 cells. Curcumin dose-dependently induced apoptosis of NTera-2 cells by reducing FasL expression and Bcl-2-to-Bax ratio, and activating caspase-9, -8 and -3. Furthermore, curcumin dose-dependently reduced the expression of AP transcription factor AP-2γ in NTera-2 cells, whereas the pretreatment with the proteasome inhibitor MG132 blocked both the curcumin-induced reduction of AP-2γ and antiproliferative effect. Curcumin inhibited ErbB2 expression, and decreased the phosphorylation of Akt and ERK in NTera-2 cells.
  
  
  CONCLUSIONS
  Curcumin induces apoptosis and inhibits proliferation in NTera-2 cells via the inhibition of AP-2γ-mediated downstream cell survival signaling pathways.
authors.affiliation: Department of Biochemistry and Molecular Biology, Key Laboratory of Protein Chemistry and Developmental Biology, Ministry of Education of China, College of Life Science, Hunan Normal University, Changsha 410081, China. zhouchang1972@126.com
authors.forename: Chang
authors.initials: C
authors.lastname: Zhou
authors.forename: Xiao-meng
authors.initials: XM
authors.lastname: Zhao
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Xiao-ting
authors.initials: XT
authors.lastname: Zhang
authors.forename: Xi-zhi
authors.initials: XZ
authors.lastname: Liu
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Ding
authors.forename: Shuang-lin
authors.initials: SL
authors.lastname: Xiang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000473:pathology; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000473:pathology; D050656:Transcription Factor AP-2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C493679:TFAP2C protein, human; D050656:Transcription Factor AP-2; D003474:Curcumin