Chemoprevention of intestinal adenomatous polyposis by acetyl‐11‐keto‐beta‐boswellic acid in APC^Min/+ mice

Abstract

Acetyl-11-keto-beta-boswellic acid (AKBA) is a derivative of boswellic acid, which is an active component of the gum resin of Boswellia serrata. AKBA has been used as an adjuvant medication for treatment of inflammatory diseases. In this study, we aimed to evaluate the efficacy of AKBA as a chemopreventive agent against intestinal adenomatous polyposis in the adenomatous polyposis coli multiple intestinal neoplasia (APC Min/1 ) mouse model. APC Min/1 mice were administered AKBA by p.o. gavage for 8 consecutive weeks. The mice were sacrificed and the number, size and histopathology of intestinal polyps were examined by light microscopy. AKBA decreased polyp numbers by 48.9% in the small intestine and 60.4% in the colon. An even greater AKBA effect was observed in preventing the malignant progression of these polyps. The number of large (>3 cm) colonic polyposis was reduced by 77.8%. Histopathologic analysis demonstrated a significant reduction in the number of dysplastic cells and in the degree of dysplasia in each polyp after AKBA treatment. There was no evidence of high grade dysplasia or intramucosal carcinoma in any of the polyps examined within the treated group. More interestingly, interdigitated normal appearing intestinal villi were observed in the polyps of the treated group. During the course of the study, AKBA was well tolerated by the mice with no obvious signs of toxicity. Results from immunohistochemical staining, Western blotting and enzyme-linked immunosorbent assay indicated that the chemopreventive effect of AKBA was attributed to a collection of activities including antiproliferation, apoptosis induction, antiangiogenesis and anti-inflammation. AKBA was found to exert its chemopreventive action through the inhibition of the Wnt/b-catenin and NF-jB/cyclooxygenase-2 signaling pathways. Our findings suggest that AKBA could be a promising regimen in chemoprevention against intestinal tumorigenesis.Colorectal cancer (CRC) is one of the leading causes of worldwide morbidity and mortality due to cancer. At least, three major forms of CRC have been described: hereditary, sporadic and colitis-associated CRC. Lifestyle factors such as diet, exercise and obesity are considered to be linked to CRC risk. CRCs are known to develop through a series of histological events, called the ''adenoma-carcinoma'' sequence. Thus, adenomatous polyps or adenomas are believed to be major precursors of CRC. 1,2 Almost half of the population will develop at least one benign adenomatous colonic polyp, and less than 3% of these cases will progress into CRCs. 3 Surgical resection and/or adjuvant therapy of early CRCs lead to a 90% 5-year survival rate. Unfortunately, only about 37% of patients are diagnosed at this early stage. 4 Thus, in addition to improving therapeutic options; better cancer prevention strategies are needed.The mutation of a tumor suppressor gene, adenomatous polyposis coli (APC), is the initiating event in both familial adenomatous polyposis (FAP) and the majority of sporadic CRC patients. Recent reports i...

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

“…Zhang et al [243] examined the effects of acetyl-11-keto-beta-boswellic acid (AKBA) and its underlying molecular mechanisms on human gastric carcinoma. AKBA is an active component of the Boswellia serrata gum resin [243,244] . In this study, AKBA significantly inhibited human gastric cancer growth without toxicity.…”

Reversal of the multidrug resistance of human ileocecal adenocarcinoma cells by acetyl-11-keto-β-boswellic acid <i>via</i> downregulation of P-glycoprotein signals

“…AKBA treatment significantly reduced polyp number and size and the degree of cytological dysplasia in the small intestine and colon (29). These effects might be produced by the inhibition of the Wnt/β-catenin and NF-κB/cyclooxygenase-2 signaling pathways.…”

The comparative study of acetyl-11-keto-beta-boswellic acid (AKBA) and aspirin in the prevention of intestinal adenomatous polyposis in APCMin/+ mice

“…gavage prevented the formation of intestinal adenomatous polyposis in APC Min/+ mice. AKBA might exert its chemopreventive action through multiple mechanisms including antiproliferation, apoptosis induction, anti-inflammation and anti-angiogenesis (12). In this study, we compared these effects of AKBA with that of aspirin in the prevention of intestinal adenomatous polyposis in APC Min/+ mice.…”

“…AKBA and aspirin were both suspended in 0.5% sodium carboxymethyl cellulose (CMC) in sterile water before application. (12). A total of 18 male mice (age, 4 weeks) were randomly divided into three groups.…”

“…Paraffin-embedded sections (4 μm thick) were cut from formalin-fixed intestinal adenomatous polyps. After deparaffinization, the immunohistochemistry staining assay was carried out as described previously (12,13). The primary antibodies included β-catenin (9562), COX-2 (4842), cyclin D1 (2922, Cell Signaling), 5-LOX (bs-0526R, Bioss, China).…”