Acetyl-11-keto-β-boswellic acid (AKBA) inhibits human gastric carcinoma growth through modulation of the Wnt/β-catenin signaling pathway

Biochim Biophys Acta. 2013 Jun;1830(6):3604-15. doi: 10.1016/j.bbagen.2013.03.003. Epub 2013 Mar 14.


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.

General significance: AKBA could be useful in the treatment of gastric cancers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Triterpenes / pharmacology*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Wnt Signaling Pathway / drug effects*
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • beta Catenin / biosynthesis
  • beta Catenin / genetics


  • Antineoplastic Agents
  • BAX protein, human
  • CCND1 protein, human
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • MYC protein, human
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-myc
  • TP53 protein, human
  • Triterpenes
  • Tumor Suppressor Protein p53
  • acetyl-11-ketoboswellic acid
  • bcl-2-Associated X Protein
  • beta Catenin
  • Cyclin D1
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9