Number Of Aberrant Crypt Foci Research Articles

Boric Acid (Boron) Attenuates AOM-Induced Colorectal Cancer in Rats by Augmentation of Apoptotic and Antioxidant Mechanisms.

Boric acid (BA) is a naturally occurring weak Lewis acid containing boron, oxygen, and hydrogen elements that can be found in water, soil, and plants. Because of its numerous biological potentials including anti-proliferation actions, the present investigates the chemopreventive possessions of BA on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Thirty laboratory rats were divided into 5 groups: negative control (A) received two subcutaneous inoculations of normal saline and nourished on 10% Tween 20; groups B-E had two injections of 15 mg/kg azoxymethane followed by ingestion of 10% Tween 20 (B, cancer control), inoculationwith intraperitoneal 35 mg/kg 5-fluorouracil injection (C, reference group), or ingested with boric acid 30 mg/kg (D) and 60 mg/kg (E). The gross morphology results showed significantly increased total colonic ACF in cancer controls, while BA treatment caused a significant reduction of ACF values. Histopathological evaluation of colons from cancer controls showed bizarrely elongated nuclei, stratified cells, and higher depletion of the submucosal glands than that of BA-treated groups. Boric acid treatment up-surged the pro-apoptotic (Bax) expression and reduced anti-apoptotic (Bcl-2) protein expressions. Moreover, BA ingestion caused upregulation of antioxidant enzymes (GPx, SOD, CAT), and lowered MDA contents in colon tissue homogenates. Boric acid-treated rats had significantly lower pro-inflammatory cytokines (TNF-α and IL-6) and higher anti-inflammatory cytokines (IL-10) based on serum analysis. The colorectal cancer attenuation by BA is shown by the reduced ACF numbers, anticipated by its regulatory potentials on the apoptotic proteins, antioxidants, and inflammatory cytokines originating from AOM-induced oxidative damage.

Proanthocyanidin and sodium butyrate synergistically modulate rat colon carcinogenesis by scavenging free radicals and regulating the COX-2 and APC pathways

BackgroundThe purpose of this study was to explore the effects of sodium butyrate (NaB), grape seed proanthocyanidin extract (GSPE), or their combination against dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) formation, which is a proxy for colon carcinogenesis in the rat colon.ResultsAfter inducing colon cancer, all treatments markedly decreased the overall numbers of ACF, with the NaB–GSPE combination eliciting the most pronounced reduction. All the treatments significantly inhibited cell proliferation as indicated by the lower percentages of Ki67-positive cells in the colonic mucosa. Also, caspase-3-immunolabeled cells were found to be significantly increased after all treatments, indicating more apoptotic activity in the initiated colonocytes. Further, the treatments significantly modulated the levels of antioxidant biomarkers, including malondialdehyde, superoxide dismutase, reduced glutathione, and total antioxidant capacity, suggesting a potently induced antioxidant activity, especially after the combination treatment. All treatments, especially the combination, dramatically downregulated the expression of COX-2 and APC, both of which are directly linked to colon cancer.ConclusionsNaB and GSPE exert potent anti-carcinogenic effects, both alone but more effectively in combination, in a rat colon cancer model. They could be important for colon cancer treatment and for adjuvant therapy in humans.

Jaboticaba (Myrciaria cauliflora) Fruit Extract Suppressed Aberrant Crypt Formation in 1,2-Dimetylhydrazine-Induced Rats.

Early intervention can significantly improve the colorectal cancer survival rate. Foods rich in phenolic compounds, such as jaboticaba (Myrciaria cauliflora), may prevent tumorigenesis. We investigated the effectivity of jaboticaba whole fruit ethanolic extract (FEX) in suppressing aberrant crypt foci (ACF), the earliest lesion of colorectal cancer (CRC), in 1,2-dimethylhydrazine (DMH)-induced rats and the underlying mechanisms related to the gut microbiota composition and short chain fatty acid (SCFA). This study was approved by the Institutional Animal Care and Use Committee (IACUC) of Providence University (Trial Registration Number 20180419A01, registration date: 22 December 2018). The FEX contains gallic acid and an especially high ellagic acid concentration of 54.41 ± 1.80 and 209.79 ± 2.49mg/100g FEX. The highest total ACF number (150.00 ± 43.86) was recorded in the DMH control (D) group. After 56 days of oral FEX treatment, the total ACF number in the low FEX dosage (DL) group was significantly lower compared to the D group (p < 0.05). The large-sized ACF (> 5 foci), which has a higher probability of progressing to later stage, was significantly decreased in the high FEX dosage (DH) group. The 16s rDNA metagenomic sequencing of the cecal material revealed that the CRC biomarker Lachnoclostridium was significantly suppressed in the DH group (p < 0.05), whereas some SCFA-producing taxa and the cecal butyrate concentration were significantly elevated in the DL and DH groups (p < 0.05). This study demonstrated the potential of jaboticaba whole fruit in CRC prevention, especially in the initial stage, by shifting gut microbiota composition and improving cecal butyrate level.

The role of TNF-α and NFkβ in an experimental model of intestinal carcinogenesis with 1,2-dimethyhydrazine.

To analyze the potential of tumor necrosis factor-α (TNF-α) and factor nuclear kappa B (NF-κB) as colorectal cancer (CRC) biomarkers in an experimental model of intestinal carcinogenesis with 1,2-dimethyhydrazine (1,2-DMH). Twenty-four male Wistar rats were divided into two groups: sham and 1,2-DMH. First, 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. Histopathological analysis, immunohistochemistry, and gene expression of TNF-α and NF-κB were performed. Statistical analysis was performed using GraphPad Prism. The location of aberrant crypt foci (ACF) was analyzed by Kruskal-Wallis' test. For analyses with two groups with parametric data, the t-test was used; for non-parametric data, the Mann-Whitney's test was used. P < 0.05 was considered significant. The number of ACF and macroscopic lesions was significantly higher (p < 0.5) in the 1,2-DMH group compared to the sham group, and most ACF were concentrated in the distal segment of the colon. There was a statistically significant increase (p < 0.5) in protein and gene expression of TNF-α and NF-κB in the 1,2-DMH group compared to the sham group. Our results provide supportive evidence that TNF-α and NF-κB pathways are strongly involved in CRC development in rats and might be used as early biomarkers of CRC pathogenesis in experimental studies.

The Effect of Low Doses of Acetylsalicylic Acid on the Occurrence of Rectal Aberrant Crypt Foci.

Background and Objectives: Aberrant crypt foci (ACF) are one of the earliest putative preneoplastic and, in some cases, neoplastic lesions in human colons. Many studies have confirmed the reduction of ACFs and colorectal adenomas after treatment with acetylsalicylic acid (ASA) commonly referred to as ASA; however, the minimum effective dose of ASA and the duration of use has not been fully elucidated. The objective of our study was to assess the significance of low dose ASA (75-mg internally once daily) to study the chemopreventive effect of ASA in ACF and adenomas development in patients taking this drug for a minimum period of 10 years. Materials and&amp;nbsp;Methods: Colonoscopy, combined with rectal mucosa staining with 0.25% methylene blue, was performed on 131 patients. The number of rectal ACF in the colon was divided into three groups: ACF &lt; 5; ACF 5-10; and ACF &gt; 10. Patients were divided into two groups: the "With ASA" group (the study group subjects taking ASA 75-mg daily for 10 years); and "Without ASA" group (control group subjects not taking ASA chronically). The incidence of different types of rectal ACF and colorectal polyps in both groups of subjects was analysed and ascertained. Results: Normal ACF was found in 12.3% in the study group vs. 87.7% control group, hyperplastic 22.4% vs. 77.6%, dysplastic 25% vs. 75%, mixed 0% vs. 100%. Treatment with ASA affects the occurrence of colorectal adenomas. The amount of dysplastic ACFs was lower in the study group than in the control group. The increase in dysplastic ACFs decreases with age in both groups, with the increase greater in those not taking ASA. Conclusions: Patients who take persistent, chronic (&gt;10 years) low doses of ASA have a lower total number of all types of rectal ACFs and adenomas compared to the control group.

Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet.

High-fat diet (HFD)-induced obesity is a risk factor for colon cancer. Our previous data show that compared to an AIN-93 diet (AIN), a HFD promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation and microbial dysbiosis in C57BL/6 mice. To explore the underlying metabolic basis, we hypothesize that AOM treatment triggers a different fecal metabolomic profile in C57BL/6 mice fed the HFD or the AIN. We found that 65 of 196 identified metabolites were significantly different among the four groups of mice (AIN, AIN + AOM, HFD, and HFD + AOM). A sparse partial least squares discriminant analysis (sPLSDA) showed that concentrations of nine fecal lipid metabolites were increased in the HFD + AOM compared to the HFD, which played a key role in overall metabolome group separation. These nine fecal lipid metabolite concentrations were positively associated with the number of colonic ACF, the cell proliferation of Ki67 proteins, and the abundance of dysbiotic bacteria. These data suggest that the process of AOM-induced ACF formation may increase selective fecal lipid concentrations in mice fed with a HFD but not an AIN. Collectively, the accumulation of these critical fecal lipid species may alter the overall metabolome during tumorigenesis in the colon.

Inhibitory Effect of Dietary Defatted Rice Bran in an AOM/DSS-Induced Colitis-Associated Colorectal Cancer Experimental Animal Model

Defatted rice bran (DRB) is gaining immense popularity worldwide because of its nutritional and functional aspects. Emerging evidence suggests that DRB is a potential source of dietary fiber and phenolic compounds with numerous purported health benefits. However, less is known about its chemoprotective efficacy. In the present study, we determined and examined the nutrient composition of DRB and its chemopreventive effect on azoxymethane and dextran sulphate sodium (AOM/DSS)-induced colitis-associated colorectal cancer (CRC) in rats. The results showed the presence of several bioactive compounds, such as dietary fiber, phytic acid, and phenolic acids, in DRB. In addition, DRB supplementation reduced the progression of CRC symptoms, such as colonic shortening, disease activity index (DAI), and histopathological changes. Interestingly, a significant decrease was observed in total numbers of aberrant crypt foci (ACFs) and tumors with DRB supplementation. Furthermore, DRB supplementation suppressed the expression of pro-inflammatory cytokines (IL-6) and inflammatory mediators (NF-κB and COX-2) through the inactivation of the NF-κB signaling pathway. The administration of DRB revealed a negative effect on cancer cell proliferation by repressing the expression of nuclear β-catenin, cyclin D1, and c-Myc. These findings suggest that DRB supplementation mitigates chronic inflammation and cancer cell proliferation and delays tumorigenesis in rat AOM/DSS-induced colitis-associated CRC. Therefore, the establishment of DRB as a natural dietary food-derived chemopreventive agent has the potential to have a significant impact on cancer prevention in the global population.

Alcohol hinders the Anti-Carcinogenic effect of Resveratrol in the Colon of rats

Resveratrol (RESV), a polyphenol present in wine and other natural sources, has potent anti-oxidant and chemopreventive effect against various types of cancer by multiple mechanisms of action. On the other hand, ethanol, which is also one important component of wine, is associated with increased oxidative stress and risk of cancer in general, including the colonic cancer. It is unknown whether the anti-oxidant and anti-carcinogenic effects of RESV could be counterbalanced by alcohol in vivo. Thus, the present study evaluated the anti-neoplastic action of RESV, pure or associated with ethanol on the colon carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in rats. It was performed a detailed analysis of aberrant crypt foci (ACF) formation and the systemic oxidative stress through malondialdehyde (MDA) dosage. The inflammatory process, which is associated to the colonic carcinogenesis, was estimated by the immune-expression of cyclooxigenase-2 (COX-2). Our experiments were performed in 32 wistar rats, divided into four groups: the group C was the control, the group M received MNNG (5mg/ml), the group MR received MNNG and RESV (1mg/kg/day) and the group MRA received RESV and alcohol (0,377g/kg/day). As a result, RESV decreased the number of ACF and COX-2 expression, but these effects were abolished by the alcohol. RESV reduced the production of MDA in all treated groups, evidencing that its systemic antioxidant effect was also present in the animals treated with alcohol. It was concluded that alcohol hindered the anti-carcinogenic effects of RESV. This effect of alcohol should be attributed to its pro-inflammatory effects, which have avoided the anti-inflammatory properties of RESV.

Deletion of cystathionine-γ-lyase in bone marrow-derived cells promotes colitis-associated carcinogenesis

Ulcerative colitis (UC) is characterized by widespread relapsing inflammation of the colonic mucosa. Colitis-associated cancer (CAC) is one of the most serious complications of a prolonged history of UC. Hydrogen sulfide (H2S) has emerged as an important physiological mediator of gastrointestinal homeostasis, limiting mucosal inflammation and promoting tissue healing in response to injury. Inhibition of cystathionine-γ-lyase (CSE)-dependent H2S production in animal models of UC has been shown to exacerbate colitis and delay tissue repair. It is unknown whether CSE plays a role in CAC, or the downregulation of CSE expression and/or activity promotes CAC development.In humans, we observed a significant decrease in CSE expression in colonic biopsies from patients with UC. Using the dextran sodium sulfate (DSS) model of epithelium injury-induced colitis and global CSE KO mouse strain, we demonstrated that CSE is critical in limiting mucosal inflammation and stimulating epithelial cell proliferation in response to injury. In vitro studies showed that CSE activity stimulates epithelial cell proliferation, basal and cytokine-stimulated cell migration, as well as cytokine regulation of transepithelial permeability. In the azoxymethane (AOM)/DSS model of CAC, the loss of CSE expression accelerated both the development and progression of CAC. The increased tumor multiplicity and severity of CAC observed in CSE-KO mice were associated with reduced levels of mucosal IL-10 expression and increased levels of IL-6. Restoring CSE expression in bone marrow (BM) cells of CSE-KO mice through reciprocal BM transplantation raised mucosal IL-10 expression, decreased IL-6 level, and reduced the number of aberrant crypt foci and tumors in AOM/DSS-treated mice.These studies demonstrate that CSE expression in BM cells plays a critical role in suppressing CAC in mice. Furthermore, the data suggest that the inhibitory effects of CSE on the development of CAC are due, in part, to the modulation of mucosal pro-and anti-inflammatory cytokine expression.

Abstract 2420: Exploring associations between the IL4 pathway and colorectal cancer risk in in vivo models and clinical records

Abstract We have previously demonstrated that inhibition of the IL4 pathway limits metastatic potential in colorectal cancers and have postulated that the type II IL4 receptor could serve as a potential target in risk assessment and treatment. Here we expand on these findings through in vivo mouse studies and retrospective patient analysis. To elucidate how colorectal cancers may use the IL4 pathway to grow and infiltrate surrounding tissue, we performed two in vivo studies independently targeting IL4ra in myeloid and intestinal epithelial tissues. Mice with a deleted allele of IL4ra and a floxed allele of IL4ra were crossed with either a line expressing a myeloid-specific Cre (LysM Cre) or an intestinal epithelial-specific Cre (Villin Cre). Our results indicate that myeloid-expressed IL4ra facilitates tumorigenesis but is not a significant contributor to later growth. In contrast, epithelial IL4ra significantly contributes to tumor number and size, but had little effect on the observed number of aberrant crypt foci, an early indicator of colon cancer. We hypothesized that effects of atypical IL4 activity could also be observed in the medical record. Atopic diseases such as asthma and eczema are characterized by an overabundance of IgE, a protein regulated by the IL4 pathway. Using Vanderbilt University Medical Center’s SD Discover program, we obtained de-identified records for patients diagnosed with at least stage II colorectal carcinoma between 2005 and 2015. We then stratified patients by metastatic progression. Patients who were diagnosed with asthma prior to age sixty were significantly less likely to develop an advanced form of colorectal cancer and at reduced risk of metastatic disease or recurrence. This may be a result of medication prescribed for atopic disease such as inhalers and corticosteroids and we are performing further analyses to test these hypotheses. Citation Format: Jacob Beckstead, Jack Petros, Kunaal Mehrotra, Barbara Fingleton. Exploring associations between the IL4 pathway and colorectal cancer risk in in vivo models and clinical records [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2420.

Effect of a Diet Supplemented with Sphingomyelin and Probiotics on Colon Cancer Development in Mice.

Previous studies have reported that dietary sphingomyelin could inhibit early stages of colon cancer. Lactic acid–producing bacteria have also been associated with an amelioration of cancer symptoms. However, little is known about the potential beneficial effects of the combined administration of both sphingomyelin and lactic acid–producing bacteria. This article analyzes the effect of a diet supplemented with a combination of the probiotics Lacticaseibacillus casei and Bifidobacterium bifidum (108 CFU/ml) and sphingomyelin (0.05%) on mice with 1,2-dimethylhydrazine (DMH)-induced colon cancer. Thirty-six BALB/c mice were divided into 3 groups: one healthy group (group C) and two groups with DMH-induced cancer, one fed a standard diet (group D) and the other fed a diet supplemented with sphingomyelin and probiotics (DS). The number of aberrant crypt foci, marker of colon cancer development, was lower in the DS. The dietary supplementation with the synbiotic reversed the cancer-induced impairment of galactose uptake in enterocyte brush–border–membrane vesicles. These results confirm the beneficial effects of the synbiotic on the intestinal physiology of colon cancer mice and contribute to the understanding of the possible mechanisms involved.

Watermelon powder supplementation reduces colonic cell proliferation and aberrant crypt foci by upregulating p21Waf1/Cip1 expression

• Watermelon supplementation inhibited colonic aberrant crypt foci (ACF) formation. • The inhibition of ACF exhibited in the proximal, middle and distal regions of colon. • Watermelon supplementation lowered colonic cell proliferation. • The decreased proliferation may related to downregulation of p21 Waf1/Cip1 expression. The objective of this study was to examine the effects of watermelon powder supplementation on colonic cell proliferation, aberrant crypt foci, and gene expression of cell cycle regulators. Thirty-two rats were randomly assigned to one of the following isocaloric diets: 0.5% watermelon powder, 0.36% l -arginine, and control for 9 weeks. All animals were injected with azoxymethane (15 mg/kg body weight s.c.). Both watermelon powder and l -arginine groups exhibited lower numbers of aberrant crypt foci (ACF) in all proximal, middle, and distal regions of the colon (P < 0.01). Both groups also showed lower proliferation index and proliferative zone (P < 0.05). In addition, watermelon powder and l -arginine supplementation upregulated p21 Waf1/Cip1 gene expression (P = 0.048). These results suggest that watermelon or l -arginine supplementation may decrease the risk of colorectal cancer as they reduced proliferation by upregulating a cyclin-dependent kinase inhibitor and inhibited ACF formation in all anatomical regions of the colon.

Effects of Scrophularia oxysepala Methanolic Extract on Early Stages of Dimethylhydrazine-Induced Colon Carcinoma in Rats: Apoptosis Pathway Approach.

Purpose: Colorectal cancer is one of the most prevalent cancers, worldwide. The present study aimed to examine the effects of Scrophularia oxysepala (SO) methanolic extract on 1,2-dimethylhydrazine (DMH) induced colon cancer model in the Wistar rats. Methods: The animals administered DMH (40 mg/kg/S.C.) biweekly for 2 weeks to induce aberrant crypt foci (ACF). Other groups of animals were given the SO extract (50, 100 and 200 mg/kg/orally once/day) either before or after the DMH treatments. In the end, all animals were killed and at necropsy, the colon samples examined. The ACF, aberrant crypt (AC), crypt multiplicity (CM), caspase 3 protein and apoptosis measurement were performed. Results: The SO extract significantly (P<0.001) decreased the number of AC, ACF, and CM in all pre- and post-treated groups and caused significant increases in caspase 3 and apoptosis as compared to the DMH group. However, post-treated animals showed significantly more effective than pre-treatment groups. Methanolic extract of SO showed a chemopreventive potential, by effectively reducing the number of AC, ACF, and CM and increasing caspase 3 protein and apoptosis. Conclusion: One of the possible mechanisms might be involved in the induction of apoptosis through the caspase 3 mediated pathway.

Protective effects of folic acid on colon carcinogenesis induced by azoxymethane in mice

Colon cancer has been considered a leading cause of cancer-associated death. Folic acid is a vitamin necessary for cellular physiological functions and cell viability. However, the association between folic acid intake and colon cancer has been examined in several prospective cohort studies are controversial. This study investigated the effects of folate intake on colon carcinogenesis and oxidative stress in an azoxymethane (AOM)/dextran sodium sulfate (DSS) institute for cancer research (ICR) mouse model. Thirty male ICR mice (5 weeks old) were divided into the control group and the experimental group supplied 0.03% folic acid via drinking water (50 mL/week/mouse) for 6 weeks. To induce colonic pre-neoplastic lesions, the animals were subcutaneously injected three times weekly with AOM (10 mg/kg body weight), followed by 2% DSS in drinking water for a week. Folic acid supplementation significantly suppressed the total number of aberrant crypt foci and aberrant crypts. Histological image data showed that folic acid supplementation attenuated neoplastic change. In addition, we measured the thiobarbituric acid reactive substances concentration of dry feces samples to identify the effect of folic acid on reactive oxygen accumulation. The folic acid supplementation group had reduced reactive oxygen species levels in dry feces compared to the control group. In conclusion, these findings indicate that folic acid suppresses colon carcinogenesis and oxidative stress in an AOM/DSS mouse model.

EPoster

Background and Aim: Aberrant crypt foci (ACF) in the rectum have been reported to correlate with the risk of colorectal tumorigenesis and are useful biomarkers for predicting the risk of colorectal cancer because they are quantitative and can be evaluated in a short period of time. Leukotriene receptor antagonists (LTRAs) have been reported to have inhibitory effects on various carcinomas, but their effects on colorectal cancer are unknown. Based on the report that colorectal cancer overexpresses the cysteinyl leukotriene receptor, we investigated whether LTRA medication affects the number of ACF. Methods: The eligibility criteria were patients who were between 30 and 80 years old, had colorectal tumors that were suitable for endoscopic resection, and had at least five ACFs in the rectum. First, 30 patients were enrolled in the LTRA group, who were treated with montelukast sodium 10 mg for 8 weeks, and rectal ACFs were counted during treatment of colorectal tumors. 10 patients in the no medication follow-up group were enrolled as the control group. Results: One patient in the control group was not examined due to the COVID-19 pandemic, so we examined 30 patients in the LTRA group and 9 patients in the control group. The number of rectal ACFs decreased to -2.4 (SD 2.2) in the LTRA group compared to baseline, while there was no decrease to 0.4 (SD 2.3) in the control group, and there was a significant difference in ACF trends between the two groups (P = 0.002). The Ki67 labeling index, which is a cell proliferation activity, was -1.34 (SD 2.68) in the LTRA group compared to baseline, while it was 0.13 (SD 1.89) in the control group, but there was no significant difference between the two groups. Conclusion: The LTRA treatment decreased rectal ACF and may reduce the risk of colorectal cancer.

A Review of Auraptene as an Anticancer Agent

Auraptene is a bioactive monoterpene coumarin isolated from Citrus aurantium and Aegle marmelos that belong to the Rutaceae family. Auraptene can modulate intracellular signaling pathways that control cell growth, inflammation and apoptosis and can exert pharmacological properties such as anti-bacterial, anti-fungal, antileishmania and anti-oxidant activity. Auraptene had inhibitory and chemo-preventive effects on the proliferation, tumorigenesis and growth of several cancer cell lines through increase in the activity of glutathione S-transferase, formation of DNA adducts and reduction of the number of aberrant crypt foci. Auraptene exhibits anticancer effects via targeting different cell signaling pathways such as cytokines, genes modulating cellular proliferation, growth factors, transcription factors and apoptosis. The present review is a detailed survey of scientific researches on the cytotoxicity and anticancer activity of Auraptene on cancer cells and tumor bearing animals.

Microencapsulated Bifidobacterium bifidum and Lactobacillus gasseri in Combination with Quercetin Inhibit Colorectal Cancer Development in ApcMin/+ Mice.

Recent studies have suggested that flavonoids such as quercetin and probiotics such as Bifidobacterium bifidum (Bf) and Lactobacillus gasseri (Lg) could play a relevant role in inhibiting colon cancer cell growth. Our study investigated the role of dietary supplementation with microencapsulated probiotics (Bf and Lg) along with quercetin in the development of mouse colorectal cancer (CRC). Methods: Adenomatous polyposis coli/multiple intestinal neoplasia (ApcMin/+) mice were fed a standard diet or the same diet supplemented with microencapsulated probiotics (Bf and Lg strains, 107 CFU/100 g food) or both probiotics strains plus microencapsulated quercetin (15 mg/100 g food) for 73 days. Changes in body and organ weights, energy metabolism, intestinal microbiota, and colon tissue were determined. The expression of genes related to the Wnt pathway was also analyzed in colon samples. Results: Dietary supplementation with microencapsulated probiotics or microencapsulated probiotics plus quercetin reduced body weight loss and intestinal bleeding in ApcMin/+ mice. An improvement in energy expenditure was observed after 8 weeks but not after 10 weeks of treatment. A supplemented diet with microencapsulated Bf and Lg reduced the number of aberrant crypt foci (ACF) and adenomas by 45% and 60%, respectively, whereas the supplementation with Bf, Lg and quercetin decreased the number of ACF and adenomas by 57% and 80%, respectively. Microencapsulated Bf and Lg in combination with quercetin could exert inhibition of the canonical Wnt/β-catenin signaling pathway in the colon of ApcMin/+ mice Conclusions: The administration of microencapsulated Bf and Lg, individually or in combination with quercetin, inhibits the CRC development in ApcMin/+ mice.

Co-administration of 5FU and propolis on AOM/DSS induced colorectal cancer in BALB-c mice

AimsCurrently, the main problems with chemotherapy are its side effects, toxicity, and drug resistance. Propolis has biological activities, such as anti-inflammatory and anti-cancer properties. This study aims to examine the combined effects of 5-fluorouracil (5FU) and propolis on colorectal cancer (CRC) in mouse models. Materials and methodsThe chemical composition of ethanolic extract of propolis was determined by gas chromatography–mass spectrometry (GC–MS). In this study, 49 male Balb/c mice (16–20 g) were divided in seven groups as a control group and experimental groups (treated and untreated CRC model [azoxymethane + dextran sodium sulfate]). This study was conducted in 8 weeks. To examine the anti-cancer effects of propolis, the number of aberrant crypt foci (ACF) was counted and the pathological lesions in the distal colonic epithelial tissue were diagnosed. In this study, the expression of beta-catenin (β-catenin), induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) proteins, which play a major role in the incidence and progression of cancer, were determined. Key findingsGC–MS analysis of propolis showed the presence of hydrocarbons, alcohols, ketones, terpenes, phenols, and flavonoids. Administering propolis in combination with 5FU reduced the number of ACFs and pathological lesions in comparison with cancer control groups (p < 0.0001) and 5FU-alone treatment (p < 0.05). The propolis combined with 5FU reduced the expression of Cox-2, iNOS, and β-catenin proteins. SignificanceThe results showed that propolis increased the efficiency of 5FU and could be taken into account as the adjunct therapy for colorectal cancer.

The Effect of Smoking on the Number and Type of Rectal Aberrant Crypt Foci (ACF)-First Identifiable Precursors of Colorectal Cancer (CRC).

Background: The problem of smoking and its influence on the occurrence of precursors and advanced colorectal cancer is often discussed in the medical literature. Tobacco smoke can provide a non-nutritional source of polycyclic hydrocarbons and other substances which, when combined with an incorrect diet, may play a role in promoting carcinogenesis at the level of the genetic control mechanism. The aim of our study was to assess the effect of smoking on the frequency and type of aberrant crypt foci (ACF) in the rectum and polyps in the large intestine in people who smoke more than 20 cigarettes a day for more than 20 years. Methods and Findings: A colonoscopy combined with rectal mucosa staining with 0.25% methylene blue was performed in 131 patients. Each of the study participants gave informed consent to participate in the study. Three bioptates were collected from the foci defined macroscopically as ACF; in cases where there were fewer foci, the number of collected foci was respectively lower. On the colonoscopy day, patients completed the questionnaire regarding epidemiological data used for analysis of factors affecting the occurrence of ACF in the study group. The number of ACF in the colon was divided into three groups: −ACF < 5, 5 < ACF < 10, ACF > 10. In the statistical analysis, numerical data were presented and real numbers, range of arrhythmic means, mean standard deviation, and results of probability distribution. The Student’s test, U test, and chi2 were applied in order to determine the significance of differences of means and frequency of events in both groups. The level of significance was set at α = 0.05. Statistica 7.1 and Excel 2010 were used. Most smokers are in the age groups between 51–70 years. In the youngest (31–40 years), single ACF appear first (ACF <5) ACF in the number of 5–10 appear a little later (around 50 years of age) and dynamically increase, reaching a maximum at the age of 60–65.ACF in the number >10 appear at the latest age (55 years old) and their number gradually increases with age (linear growth). The probability of occurrence of ACF in all groups is greater in smokers, and the difference for the ACF group 5-10 and ACF >10 is statistically significant with a significance level of p < 0.05. Apart from ACF normal, all types of ACF are more likely in this group than in non-smokers and these differences are statistically significant with p < 0.05. Conclusions: Smoking has a significant impact on the number and type of rectal ACF. Smokers have a greater number of ACFs in the rectum than non-smokers, and the most common type is hyperplastic ACF. Smokers are more likely to develop polyps in all sections of the colon compared to non-smokers.

Effect of ascorbic acid and hemin on experimental colon carcinogenesis in mice

Colon cancer is known as the third most widespread cancer in the world. The interaction of heme-iron and ascorbic acid (AA) in colon carcinogenesis is not evident. Hemin (ferric chloride heme) is an iron-containing porphyrin with chlorine that can be formed from a heme group. The purpose of this study was to investigate the protective effect of AA on the formation of pre-neoplastic lesions induced by azoxymethane (AOM)/dextran sodium sulfate (DSS) plus hemin in mice. Forty-five ICR male mice were divided into three experimental groups; AOM/ DSS treatment (control group), hemin (2 g hemin/kg of b.w.), hemin + AA (1.0% in drinking water). The mice had three s.c. injections (0–2nd weeks of the experiment) of AOM (10 mg/kg b.w.) weekly and 2% DSS as drinking water for the next one week and the animals fed on AIN-76A purified rodent diet for 6 weeks. The numbers of aberrant crypt foci (ACF) and aberrant crypts (ACs) in colonic mucosa were counted after methylene blue staining. Lipid peroxidation in feces was measured by the thiobarbituric acid-reactive substances (TBARS) assay. The numbers of ACF and ACs per colon significantly increased in Hemin group compared to the control group. However, the numbers of ACF and ACs per colon notably decreased in hemin + AA group compared to the control group or hemin group (p&lt;0.05). In feces, the TBARS value of hemin group was higher than the control group (p&lt;0.01). The TBARS value of hemin + AA group was slightly decreased compared to Hemin group. These results indicate that hemin can promote the experimental colon carcinogenesis in ICR mice. On the other hand, additional supplement of AA via drinking water has a protective effect against the colon carcinogenesis. The related mechanisms need to be illustrated by further studies in future.