Format

Send to

Choose Destination

RETRACTED ARTICLE

See: Retraction Notice

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

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

Author information

1
Department of Pharmacology, Shandong University, Jinan, China.

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.

GENERAL SIGNIFICANCE:

AKBA could be useful in the treatment of gastric cancers.

PMID:
23500016
DOI:
10.1016/j.bbagen.2013.03.003
[Indexed for MEDLINE]

Publication types, MeSH terms, Substances

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center