Evaluation of Chemopreventive Effects of Acanthus ilicifolius against Azoxymethane-Induced Aberrant Crypt Foci in the Rat Colon

Abstract

Background Acanthus ilicifolius, a mangrove medicinal plant, is traditionally used to treat a variety of diseases. The aim of this research is to assess the chemoprotective outcomes of A. ilicifolius ethanolic extract against azoxymethane (AOM) induced colonic aberrant crypt foci (ACF) in rats.Methodology/Principal FindingsIn our study, rats were arranged in to five groups. Rats in the normal control group were given subcutaneous injections of normal saline once weekly for 2 weeks. The AOM control, reference and treatment groups were given subcutaneous injection of AOM, 15 mg/kg body weight, once weekly for 2 weeks each. The reference group was treated with 35 mg/kg 5-Fluorouracil via intraperitoneal injection once weekly for 8 weeks, and the treatment groups were administered by gavage with 250 and 500 mg/kg A. ilicifolius extract daily for 8 weeks. Both normal and AOM control groups received the vehicle; 10% Tween-20 only.Rats treated with 250 mg/kg and 500 mg/kg of A. ilicifolius extracts showed a decrease in the mean number of ACF by 65% and 53%, respectively. Those fed with A. ilicifolius showed significantly decreased multiplicity of ACF formations when compared with the results from the AOM control group. The 250 mg/kg A. ilicifolius treatment group showed significant decreases in lipid peroxidation MDA levels when compared with the AOM control group. In immunohistochemistry staining, the proliferating nuclear cell antigen (PCNA)-positive cells were significantly higher in the AOM control group than in the A. ilicifolius-treated groups. RT-PCR showed that A. ilicifolius caused a change in the regulation of apoptosis-related genes expression.Conclusion/SignificanceThe results of the current study show that AOM-treated rats receiving oral exposure to A. ilicifolius demonstrated a significant decrease in the number of ACF in the colon when compared to AOM-treated rats receiving vehicle only. A ilicifolius may be an effective herbal approach for the prevention of AOM-induced ACF in the rat colon.

Extract of the Bark of Bathysa cuspidataAttenuates the Development of Chemically-Induced Preneoplastic Colorectal Lesions in Rats

“…Phenolic compounds were the predominant antioxidant constituents in G. procumbens. A similar result was found by Almagrami et al (2014) in the rats with induced colorectal cancer and treated with the ethanolic extract of Acanthus ilicifolius (250 and 500 mg/kg body weight) for eight weeks. Polyphenols and flavonoids may inhibit the carcinogenesis by affecting the molecular events in the initiation, promotion, and progression stages.…”

Inhibitory Activity of Indonesian Soybean in comparison with Soybean Meal on Goblet Cell Count and Micro Vessel Density in Colitis-Associated Mouse Colon Carcinogenesis

“…Goblet cells are largely responsible for secreting components of the intestinal mucosal barrier and represent a major cellular component of the innate defense system Goblet cell clearly marked the severity of intestinal inflammation 22, 43 . The number of goblet cell is known decreased obviously in aberrant crypt foci, an earlier marker of colon carcinogenesis 25,44, 45 .…”

Paricalcitol Enhances the Chemopreventive Efficacy of 5-Fluorouracil on an Intermediate-Term Model of Azoxymethane-Induced Colorectal Tumors in Rats

“…On the other hand, the potential antitumor properties of paricalcitol, a synthetic less calcemic vitamin D analogue directly activates VDR, have recently attracted a specific deal of attention (9,10,(13)(14)(15)(16). Herein, an intermediate-term (15 weeks) model of colorectal tumorigenesis was induced in rats by AOM, a commonly used in vivo model for the experimental study of human colorectal cancer at several aspects (18)(19)(20); our study was designed to investigate the chemopreventive efficacy of paricalcitol and 5-FU alone and in combination, and whether their cotherapy resulted in an enhanced chemopreventive effect than individual therapy on this model. Interestingly, in comparison with their monotherapy, cotherapy with paricalcitol and 5-FU had resulted in augmenting effects in inhibiting the formation .…”

“…For induction of colorectal tumorigenesis, AOM was dissolved in normal saline and injected subcutaneously at a dose of 15 mg/kg, once weekly for 2 weeks as described previously (18). According to the subsequent treatment schedules, the rats were randomly categorized into the following 5 groups (15 rats/ group): group 1 (normal controls): received only normal saline; group 2 (AOM group): AOM-injected rats and left without treatment; group 3 (5-FU group): AOM-injected rats and then treated with 5-FU; group 4 (paricalcitol group): AOM-injected rats and then treated with paricalcitol; and group 5 (5-FUþ paricalcitol group): AOM-injected rats and then treated with 5-FU plus paricalcitol combination therapy.…”

“…Therefore, the current study was aimed to investigate whether paricalcitol would improve and synergize the anti-colorectal cancer effect of 5-FU, and to identify the possible mechanisms underlying such synergy on an intermediate-term model of colorectal neoplasia induced by azoxymethane (AOM) in rats. AOM-induced colorectal tumors and carcinogenesis in rats and mice have been proven as an outstanding rodent model that closely mirror the phases and features of human colorectal cancer [aberrant crypts foci (ACF)-adenoma-adenocarcinoma and carcinoma sequence] in a timedependent manner post-AOM injection, and commonly used to assess new chemopreventive and therapeutic strategies and to provide new insights into the pathophysiologic mechanisms and risk factors of human colorectal cancer (18)(19)(20). Our findings showed that monotherapy with either 5-FU or paricalcitol resulted in a significant chemopreventive effect on this model; however, their combination exhibited a more significant efficacy to repress the morphologic, histopathologic, and molecular changes that were observed in this model.…”