title: Antiproliferative activity of rosamultic acid is associated with induction of apoptosis, cell cycle arrest, inhibition of cell migration and caspase activation in human gastric cancer (SGC-7901) cells.
abstract: BACKGROUND
  Gastric cancer is the second leading cause of cancer related deaths after lung cancer globally. Among natural products, natural triterpenes represent a structurally diverse group of organic compounds with potent antitumor activity.
  
  
  OBJECTIVE
  The objective of the present research work demonstrated the antiproliferative and apoptotic activity of rosamultic acid, a natural triterpenoid, in human gastric cancer (SGC-7901) cells. Its effect on cellular morphology, cell cycle arrest, DNA fragmentation and expression levels of caspase-3, caspase-8 and caspase-9 were also determined.
  
  
  METHODS
  Antiproliferative activity of rosamultic acid was evaluated by MTT assay. Phase contrast, fluorescence microscopy as well as flow cytometry using Hoechst 33342, acridine orange/ethidium bromide and Annexin V-FITC as cellular probes were used to evaluate the induction of apoptosis by rosamultic acid. Protein level expressions were analyzed by western blot analysis.
  
  
  RESULTS
  The results revealed that rosamultic acid induced dose-dependent as well as time dependent cytotoxic effects in SGC-7901 gastric cancer cells. It also led to a reduction in clonogenic activity along with inhibiting the cell migration. Characteristic features of apoptosis induced by rosamultic acid were observed and quantified. Cell cycle arrest at sub-G1 phase was induced by rosamultic acid along with downregulation of expression levels of CDK4, CDK6 and cyclin D1. Rosamultic acid also significantly led to the activation of caspase-3, -8 and -9 during the 48 h treatment along with cleaving PARP in a dose-dependent manner. DNA fragmentation following rosamultic acid treatment was also observed in these cells.
  
  
  CONCLUSIONS
  The current study strongly reveals that rosamultic acid inhibits gastric cancer proliferation by inducing apoptosis mediated through cell cycle arrest, downregulation of cell cycle related protein expressions, inhibition of cell migration, DNA damage, and activation of caspases.
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, No. 155 North of Nanjing Street, Heping District, Shengyang City Liaoning 110001, China. Electronic address: chengguangsui@gmail.com.
authors.forename: Cheng-Guang
authors.initials: CG
authors.lastname: Sui
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, No. 155 North of Nanjing Street, Heping District, Shengyang City Liaoning 110001, China.
authors.forename: Fan-Dong
authors.initials: FD
authors.lastname: Meng
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, No. 155 North of Nanjing Street, Heping District, Shengyang City Liaoning 110001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Hospital of China Medical University, No. 155 North of Nanjing Street, Heping District, Shengyang City Liaoning 110001, China.
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Jiang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018517:Plant Roots / Q000737:chemistry; D027826:Rosa / Q000737:chemistry; D013274:Stomach Neoplasms / Q000473:pathology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D014315:Triterpenes; C000601975:rosamultic acid; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
keywords: Apoptosis; Caspases; Cell cycle; Gastric cancer; Rosamultic acid