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| Background: Acetyl-11-keto-beta-boswellicacid (AKBA) is a derivative of boswellic acid, which is an active component of gum resin of Boswellia serrata. AKBA has been used as drug to treatment of inflammatory diseases like inflammatory bowel disease, rheumatoid arthritis, osteoarthritis etc. In this study, we aimed to examine the effect of AKBA on human gastric carcinoma growth, and to explore the underlying molecular mechanisms.
Methods: Inhibition of cancer growth was estimated by colorimetric and clonogenic assays. Cell cycle was analyzed by FACScan flow cytometer. The apoptotic cells were determined by Annexin V-FITC/PI staining and DNA ladder quantification. Further experiment was performed in mice bearing human cancer xenografts. After 3 weeks oral administration, mice were sacrificed and the xenografts were removed for TUNEL staining and Western blotting analysis.
Results: AKBA significantly inhibited cancer growth as determined in vitro and in mice. Oral AKBA in mice effectively delayed the growth of SGC-7901 xenografts without toxicity. The inhibition of AKBA on cancer growth was associated with its activity in cell cycle arrest and apoptosis induction, showing the activation of p21Waf1/Cip1 and p53 in mitochondria. More evidences included the increase of cleaved caspase-9, caspase-3 and cleaved PARP, and also the Bax/Bcl-2 ratio in AKBA-treated cells. Further analysis suggested that AKBA could impair the β-catenin-dependent expression of signals, showing decrease of β-catenin in nuclei and increase of β-catenin in membrane. Consequently, GSK3β was activated and the expressions of cyclin D1, PCNA, survivin, c-Myc, MMP-2 and MMP-7 were inhibited.
Conclusions: AKBA inhibited human gastric carcinoma growth, possibly due to modulation of the Wnt/β-catenin signaling pathway. AKBA could be a useful agent in treatment of gastric cancers. |
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| Keywords:Gastric carcinoma; Acetyl-11-keto-β-boswellic acid (AKBA); Inhibitory effect; Apoptosis; the Wnt/β-catenin pathway |
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