title: Maslinic acid activates mitochondria-dependent apoptotic pathway in cardiac carcinoma.
abstract: OBJECTIVE
  Cardiac carcinoma is the most common subtype of gastric cancer and its incidence has increased in recent years. The current chemotherapeutic drugs exhibit limited effectiveness and significant side effects in patients. Maslinic acid (MA) exerts an anti-tumor activity on a wide range of cancers and has no significant side effect; however, the anti-tumor effect of MA on cardiac carcinoma has not yet been explored.
  
  
  METHODS
  MTT assays, tumor xenograft animal model, immunoblotting, MMP assessment and flow cytometry were performed in this study.
  
  
  RESULTS
  MA was able to suppress the viability of cardiac carcinoma cells in both a time- and dose-dependent manner. This natural compound exhibited no cytotoxicity in normal cells. Its inhibitory effect on tumor growth was further confirmed in a mouse model. Mechanistically, MA induced the activation of p38 MAPK in cardiac carcinoma cells and, in turn, changed their mitochondrial membrane potential (MMP). Finally, caspase cascades were activated by a series of cleavages, leading to apoptosis in cardiac cancer cells. Inhibition of p38 MAPK signaling was able to rescue the effect of MA on cardiac carcinoma cells.
  
  
  CONCLUSIONS
  Our data demonstrated that natural compound, MA, suppressed the growth of cardiac carcinoma by inducing apoptosis via the p38 MAPK/mitochondria/caspase pathway. MA and its derivatives may be promising anti-tumor agents for cardiac carcinoma treatment in the future. (Supplemental Figures available here.).
authors.forename: Tingmin
authors.initials: T
authors.lastname: Chang
authors.forename: Xiumin
authors.initials: X
authors.lastname: Li
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Chen
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Zhenjuan
authors.initials: Z
authors.lastname: Li
authors.affiliation: . Jianshenglihn@gmail.com.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D006338:Heart Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D009828:Oleanolic Acid / Q000031:analogs & derivatives
chemical_list: D000970:Antineoplastic Agents; D014315:Triterpenes; C412811:maslinic acid; D009828:Oleanolic Acid