title: Acetyl-11-keto-β-boswellic acid (AKBA) inhibits human gastric carcinoma growth through modulation of the Wnt/β-catenin signaling pathway.
abstract: BACKGROUND
  Acetyl-11-keto-beta-boswellic acid (AKBA) is a derivative of boswellic acid, an active component of Boswellia serrata gum resin. We examined the effect of AKBA on human gastric carcinoma growth and explored the underlying molecular mechanisms.
  
  
  METHODS
  Inhibition of cancer cell growth was estimated by colorimetric and clonogenic assays. Cell cycle distribution was analyzed by flow cytometry and apoptosis determined using Annexin V-FITC/PI staining and DNA ladder quantification. After three weeks of oral AKBA administration in nude mice bearing cancer xenografts, animals were sacrificed and xenografts removed for TUNEL staining and western blot analysis.
  
  
  RESULTS
  AKBA exhibited anti-cancer activity in vitro and in vivo. With oral application in mice, AKBA significantly inhibited SGC-7901 and MKN-45 xenografts without toxicity. This effect might be associated with its roles in cell cycle arrest and apoptosis induction. The results also showed activation of p21(Waf1/Cip1) and p53 in mitochondria and increased cleaved caspase-9, caspase-3, and PARP and Bax/Bcl-2 ratio after AKBA treatment. Further analysis suggested that these effects might arise from AKBA's modulation of the aberrant Wnt/β-catenin signaling pathway. Upon AKBA treatment, β-catenin expression in nuclei was inhibited, and membrane β-catenin was activated. In the same sample, active GSK3β was increased and its non-active form decreased. Levels of cyclin D1, PCNA, survivin, c-Myc, MMP-2, and MMP-7, downstream targets of Wnt/β-catenin, were inhibited.
  
  
  CONCLUSIONS
  AKBA effects on human gastric carcinoma growth were associated with its activity in modulating the Wnt/β-catenin signaling pathway.
  
  
  CONCLUSIONS
  AKBA could be useful in the treatment of gastric cancers.
authors.affiliation: Department of Pharmacology, Shandong University, Jinan, China.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Zhang
authors.forename: Ji-Zhen
authors.initials: JZ
authors.lastname: Xie
authors.forename: Julia-Li
authors.initials: JL
authors.lastname: Zhong
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.forename: Rui-Qi
authors.initials: RQ
authors.lastname: Wang
authors.forename: Yi-Zhuo
authors.initials: YZ
authors.lastname: Qin
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Lou
authors.forename: Zu-Hua
authors.initials: ZH
authors.lastname: Gao
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Qu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014315:Triterpenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C489427:MYC protein, human; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc; C495901:TP53 protein, human; D014315:Triterpenes; D016159:Tumor Suppressor Protein p53; C094432:acetyl-11-ketoboswellic acid; D051028:bcl-2-Associated X Protein; D051176:beta Catenin; D019938:Cyclin D1; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9