Colon Cancer Prevention Research Articles

Abstract IA016: Vaccine approach for the interception of colon cancer

Abstract This year, in the US, an estimated 150,000 people will be diagnosed with colon cancer and ~52,000 will die of the disease. A vaccine approach is well suited to colon cancer prevention. First, a limited number of immunizations can be given over a short period of time to achieve a desired immune response. If immunologic memory develops, antigen specific T-cells will persist in the body for years, ready to be deployed when aberrant cells are detected. Finally, there are several well-defined high-risk populations that would be suitable for testing a preventative colon cancer vaccine including individuals (1) with a hereditary genetic syndrome such as familial adenomatous polyposis, (2) with a history of inflammatory bowel disease such as Crohn’s disease or ulcerative colitis, and (3) those with a history of hyperplastic colonic polyps. Vaccines targeting virally mediated cancers are effective, in part, because T-cells are primed to proteins involved in oncogenesis. The most common type of colon adenoma and invasive cancer associated antigens are non-mutated growth-related proteins that become markedly overexpressed in the disease state. Genes which are aberrantly up-regulated and conserved from adenoma to invasive colon carcinoma may encode overexpressed proteins that are associated with colon cancer initiation. Evaluating gene expression data derived from over 600 colorectal cancers, matched normal tissues, and colon adenomas we identified 160 genes overexpressed in the majority of adenomas and early-stage colon cancers, but not in normal tissues. Using siRNA screening we demonstrated 35 of those genes, when silenced, resulted in apoptosis or inhibition of growth of colon cancer cells and an adenoma cell line but not a non-neoplastic colon cell line. Of those genes, 16 have been shown to encode proteins that are overexpressed in both adenomas and colon cancer and are associated with disease progression and over a third of these proteins are immunogenic. These proteins could serve as potential candidate antigens for inclusion in a multi-antigen vaccine. Recently, we have identified epitopes within the natural sequences of non-mutated tumor antigens that only generate Th1 (Th1 selective) antigen specific T-cells. This discovery and the development of high throughput methods to both identify and screen putative Class II binding peptides for Th selective function has allowed us to develop antigen specific Th1 selective vaccines. A vaccine targeting CDC25B, COX2, and EGFR can inhibit intestinal tumor formation in both APCmin mice and mice with tumor induced by AOM. Concomitant use of NSAIDs potentiates the immune response generated with vaccination. The anti-tumor response observed after vaccination is significantly correlated with elevated CD8 T-cells found in the lesions and induced by immunization as well as high magnitude antigen specific T-cells identified in the spleen. These data validate a genomic approach to antigen discovery and anti-tumor efficacy of Th1 selective vaccines for colon cancer prevention. Citation Format: Mary Disis, Ying Liu, Lauren Corulli, Erin Rodmaker, Denise Cecil. Vaccine approach for the interception of colon cancer. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr IA016.

Physico-chemical analysis of newly prepared prebiotic chocolates by using Galacto Oligosaccharides (GOS)

In India, chocolate is very famous mood freshening sweet food product specially for children. But high consumption of chocolate may be harmful for human health, because most of the chocolates contain high fat. This research has been done to increase the health benefits of chocolate by using cocoa and Galacto Oligosaccharides (GOS). Many researchers have shown their research that GOS is very beneficial for human health such as it helps to lower down the cholesterol levels in the blood, to prevent colon cancer, and helps to improve mineral absorption in human body. Basically, GOS is a type of prebiotic e.g., food for probiotic bacteria. Prebiotics are non-digestible ingredients that benefit the host by boosting the growth and activity of one or a few bacterial species that are already present in the colon. It was also studied by many researchers that cocoa powder contains a lot of caffeine, flavanols, which are polyphenolic compounds. Flavanols, particularly epicatechin monomer and oligomer cocoa flavanols have been linked to a number of health advantages, including boosting nitric oxide synthase, enhancing blood flow and arterial flexibility, lowering blood pressure and platelet aggregation, and reducing inflammation. The main objectives of this research are to develop the formulation of prebiotic chocolate and to evaluate the physicochemical parameters of the newly prepared chocolate. After physico-chemical analysis of carbohydrate, fat, crude fibre and pH, it was found that both the newly prepared prebiotic enriched chocolates (T1 and T2) were significantly different (p≤0.01) from control (T0) and after analysis of protein content, it was also found that both the newly prepared prebiotic enriched chocolates (T1 and T2) were insignificantly different (p≤0.01) from control (T0).

Ameliorative and protective activity of Silver Nanoparticles (AgNPs) Biosynthesized Using Taraxacum officinale L. leaves Extract against 1, 2-dimethylhydrazine (DMH) Induced Colon Cancer in Rats

Colorectal cancer (CRC) is one of the most frequent cancers worldwide and the leading cause of death annually. In recent years, the study of natural preventative agents and food components in addition to traditional treatments has seen an increase in interest and effort. Nowadays, novel procedures are constantly being researched, including nanotechnology-based cancer treatment, which is regarded as one of the most promising research directions for colon cancer. This experiment's goal was to determine if silver nanoparticles made from aqueous extracts of Taraxacum officinale leaves (TOL-AgNPs) could help prevent colon cancer in rats that had been given 1,2-dimethylhydrazine (DMH). Thirty-five rats have been allocated at random into five groups: control, DMH, TOL-AgNPs alone, TOL-AgNPs combined with DMH, and post-treated. DMH was administered intraperitoneally at a dosage of 30 mg/kg body weight once per week for eight weeks, while TOL-AgNPs were orally given at a dosage of 20 mg/kg body weight. UV-visible spectroscopy, FTIR spectrum, X-ray diffraction (XRD), SEM and EDAX, TEM examinations were utilized to characterize TOL-AgNPs. Hematological and biochemical tests were assessed additionally for markers of oxidative stress. Also, colon tissues were examined histopathologically. It was discovered that DMH elevated the hematological and biochemical parameters significantly (P≤0.05). TOL-AgNPs restored these measurements to an approximately normal range. According to a histopathological examination, the TOL-AgNPs exhibit anticancer effects in all nano-extract treatment groups. Our findings demonstrated that AgNPs produced utilizing the leaves of T. officinale have potent anticancer activity against DMH-induced colon cancer.

Anticancer Properties of Saccharomyces boulardii Metabolite Against Colon Cancer Cells.

Saccharomyces cerevisiae var. boulardii has been used as a probiotic yeast in the medical and food industries. Colon cancers have been known as the third most common cancer type worldwide. Nowadays, cell-free extract and metabolites of probiotics have been employed for the treatment or prevention of different cancer diseases. This study investigates the anticancer properties of S. boulardii metabolites against human colon carcinoma. We evaluated cytotoxicity, apoptosis induction, and suppression of survivin, IL-8, and NFƙB gene expression effects of SBM against caco-2 cells after 24 and 48h. IC50 concentrations of SBM were measured at 815 and 1411µg/mL for 24 and 48h treatments, respectively. The total proportion of apoptotic caco-2 cells treated with SBM after 24 and 48h were calculated at 62.23 and 88.7%, respectively. Also, relative expression of survivin, IL-8, and NFƙB genes were significantly suppressed in caco-2 cells treated with SBM after 24 and 48h. In conclusion, we found that SBM induced apoptosis, inhibited the growth rate, and suppressed the expression of the survivin, IL-8, and NFƙB genes in human colorectal cancer cells and it can be considered as a perspective supplement or drug for the treatment or prevention of colon cancer in humans.

A comprehensive review on RNA interference-mediated targeting of interleukins and its potential therapeutic implications in colon cancer.

Colon cancer is the world's fourth leading cause of death. It is cancer of the latter part of the large intestine, i.e. the colon. Chronic inflammation over a long period also leads to the development of cancer. Cancer in the colon region is arduous to diagnose and is detected at a later stage when it metastasizes to other parts of the body like the liver, lungs, peritoneum, etc. Colon cancer is a great example of solid tumours associated with chronic inflammation. Although conventional therapies are effective, they lose their effectiveness beyond a certain point. Relapse of the disease occurs frequently. RNA interference (RNAi) is emerging as a great tool to specifically attack the cancer cells of a target site like the colon. RNAi deals with epigenetic changes made in the defective cells which ultimately leads to their death without harming the healthy cells. In this review, two types of epigenetic modulators have been considered, namely siRNA and miRNA, and their effect on interleukins. Interleukins, a class of cytokines, are major inflammatory responses of the body that are released by immune cells like leukocytes and macrophages. Some of these interleukins are pro-inflammatory, thereby promoting inflammation which eventually causes cancer. RNAi can prevent colon cancer by inhibiting pro-inflammatory interleukins.

Inhibition of Colon Cancer Cells Via Apoptosis Pathway by Ethanolic Extract of Andaliman (Zanthoxylum Acanthopodium Dc.) Fruits

Andaliman (Zanthoxylum acanthopodium DC.) is an exotic spice from North Sumatra (Indonesia) commonly added to enrich the flavor of Bataknese ethnic food because of its unique aroma and trigeminal sensation. Traditionally, it is also known to have health benefits in the gastrointestinal tract; however no studies have reported it. Therefore, this study aimed to investigate the potency of Andaliman fruit to inhibit the proliferation of HCT-116 and WiDr colon cancer cells and its underlying mechanism of inhibition. Andaliman fruits were extracted using ethanol. The anti-proliferative effect was evaluated using the MTT test, and the underlying mechanism of inhibition was examined using the Real-Time Polymerase Chain Reaction (RT-PCR) and Hoechst staining. Bax and Bcl-2 proteins were used as the markers for the pro-apoptotic and anti-apoptotic gene expression analysis, respectively. Andaliman ethanolic extract showed potential bioactivity to inhibit the growth of WiDr and HCT-116 cells in vitro with IC50 of 95.61 μg.mL-1 and 94.64 μg.mL-1, respectively. The cytotoxicity effect of andaliman was rationalized by the gene expression of Bax and Bcl-2 in a non-dose-dependent manner. In addition, Andaliman extract could increase the apoptotic gene marker expression in both cells at half of their IC50, i.e. 47.81 μg.mL-1 and 47.32 μg.mL-1 for WiDr and HCT-116 cells, respectively. This study demonstrated that Andaliman fruit could be potentially developed as a functional food ingredient to prevent colon cancer by inducing the apoptosis mechanism.

Therapeutic Potential of 6-Gingerol in Prevention of Colon Cancer Induced by Azoxymethane through the Modulation of Antioxidant Potential and Inflammation.

A polyphenolic component of ginger, 6-gingerol, is widely reported to possess antioxidant, anti-inflammatory and anticancer activities. In the current study, it was aimed to investigate the anticancer effects of 6-gingerol (6-Gin) on azoxymethane (AOM)-induced colon cancer in rats. The results reveal that 6-Gin treatment significantly improves the antioxidant status disturbed by AOM intoxication. The 6-Gin treatment animal group showed enhanced activity of catalase (CAT) (46.6 ± 6.4 vs. 23.3 ± 4.3 U/mg protein), superoxide dismutase (SOD) (81.3 ± 7.6 vs. 60.4 ± 3.5 U/mg protein) and glutathione-S-transferase (GST) (90.3 ± 9.4 vs. 53.8 ± 10 mU/mg protein) (p < 0.05) as compared to the disease control group. Furthermore, the results reveal that AOM significantly enhances the inflammatory response and 6-gingerol potentially attenuates this response, estimated by markers, such as tumor necrosis factor-α (TNF-α) (1346 ± 67 vs. 1023 ± 58 pg/g), C-reactive protein (CRP) (1.12 ± 0.08 vs. 0.92 ± 0.7 ng/mL) and interleukin-6 (IL-6) (945 ± 67 vs. 653 ± 33 pg/g). In addition, the lipid peroxidation estimated in terms of malondialdehyde (MDA) provoked by AOM exposure is significantly reduced by 6-gingerol treatment (167 ± 7.5 vs. 128.3 nmol/g). Furthermore, 6-gingerol significantly maintains the colon tissue architecture disturbed by the AOM treatment. Loss of tumor suppressor protein, phosphatase and tensin homolog (PTEN) expression was noticed in the AOM treated group, whereas in the animals treated with 6-gingerol, the positivity of PTEN expression was high. In conclusion, the current findings advocate the health-promoting effects of 6-gingerol on colon cancer, which might be due to its antioxidant and anti-inflammatory potential.

Abstract IA018: Microbiome and intestinal barriers in colon cancer

Abstract Multiple factors (e.g., risk genes, environmental triggers, immunity, and microbiome) contribute to the pathogenesis of colorectal cancer (CRC). The intestinal dysbiosis and disruption of barrier function are common manifestations of CRC. Vitamin D/Vitamin D receptor (VDR) is known to protects against dysbiosis and tumorigenesis. Considering the multiple functional roles of VDR in the development of cancer, it is important to dissect the mechanisms by which host factors contribute to the intestinal barrier function in protecting cells from tumorigenesis. Here, we reported that in human tissue, reduced VDR in the colon of CRC patients is associated with the reduced intestinal barrier and enhanced bacterial translocation to tumors. VDR deficiency in the intestinal epithelial cells led to the reduced thickness of mucus layer and enhanced penetration of microbiota into the epithelial cells. VDR was a transcriptional factor regulating the genes of some tight junction (TJ) Claudins. The positively correlated status of VDR and Claudins (e.g., Claudin- 5 and10) contribute to the altered intestinal permeability in tumorigenesis. In the intestinal epithelial VDR conditionally knockout VDR∆IEC mice and myeloid VDR deletion mice, dysbiosis and inflammatory cytokines in the VDR deficient context further altered TJ proteins and manipulated the barrier functions in the development of colon cancer. Furthermore, we found that mice with colonic adenomatous polyposis coli (APC) mutation reduced thickness of mucus layer and enhanced penetration of microbiota into the epithelial cells, thus enhancing tumorigenesis in the colon. Studies on host factor regulation of microbiome and barriers could be potentially applied to risk assessment, early detection, and prevention of colon cancer. These studies will provide an additional avenue to restore microbiome and barrier functions for risk assessment and prevention of CRC and other cancers. Citation Format: Jun Sun, Jilei Zhang, Yinglin Xia, Yong-Guo Zhang. Microbiome and intestinal barriers in colon cancer [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr IA018.

Nobiletin is capable of regulating certain anti-cancer pathways in a colon cancer cell line.

Natural remedies have the potential to improve conventional cancer therapies and enhance patient outcomes. Citrus polymethoxyflavone nobiletin has been demonstrated to have anticancer effects on several cancer cell lines. In this study, the anti-cancer activity of nobiletin is investigated on Bax, Bcl-2, HO-1, VEGF, MMP-7, Akt, p70S6K, 4EBP1, tuberin, and hamartin. IC50 doses were 403.6µM, 264µM, and 40µM, respectively, at 24, 48, and 72h. Akt, Bax, Bcl-2, and p70S6K levels decreased at nobiletin concentrations greater than 100, 250, 500, and 1000µM, respectively. Nobiletin decreased HO-1 and VEGF levels at concentrations greater than 100µM. MMP-7 levels interestingly increased at 100µM but decreased at doses greater than 250µM. 4EBP1 levels increased, except from 2000 and 3000µM nobiletin concentrations. Tuberin levels increased at 10, 50, and 3000µM, decreased at 250µM, and remained unchanged at the rest of the concentrations. Nobiletin decreased hamartin levels; however, this decrease was statistically significant only at 10, 100, 250, 500, and 3000µM concentrations. Decreased Akt activity might be interpreted as nobiletin inhibiting mTORC1 activity and subsequently increased 4EBP1 and unchanged or decreased p70S6K protein levels. Akt activity can cause suppression of angiogenesis via decreased VEGF, MMP-7, and HO-1 levels at concentrations greater than 500µM. These results are significant as a nobiletin therapy could prevent colon cancer progression by inhibiting Akt signaling and angiogenesis.

CXCL1 promotes colon cancer progression through activation of NF-κB/P300 signaling pathway

BackgroundThe upregulated expression of CXCL1 has been validated in colorectal cancer patients. As a potential biotherapeutic target for colorectal cancer, the mechanism by which CXCL1 affects the development of colorectal cancer is not clear.MethodsExpression data of CXCL1 in colorectal cancer were obtained from the GEO database and verified using the GEPIA database and the TIMER 2.0 database. Knockout and overexpression of CXCL1 in colorectal cancer cells by CRISPR/Cas and "Sleeping Beauty" transposon-mediated gene editing techniques. Cell biological function was demonstrated by CCK-8, transwell chamber and Colony formation assay. RT-qPCR and Western Blot assays measured RNA and protein expression. Protein localization and expression were measured by immunohistochemistry and immunofluorescence.ResultsBioinformatics analysis showed significant overexpression of CXCL1 in the colorectal cancer tissues compared to normal human tissues, and identified CXCL1 as a potential therapeutic target for colorectal cancer. We demonstrate that CXCL1 promotes the proliferation and migration of colon cancer cells and has a facilitative effect on tumor angiogenesis. Furthermore, CXCL1 elevation promoted the migration of M2-tumor associated macrophages (TAMs) while disrupting the aggregation of CD4+ and CD8+ T cells at tumor sites. Mechanistic studies suggested that CXCL1 activates the NF-κB pathway. In the in vivo colon cancer transplantation tumor model, treatment with the P300 inhibitor C646 significantly inhibited the growth of CXCL1-overexpressing colon cancer.ConclusionCXCL1 promotes colon cancer development through activation of NF-κB/P300, and that CXCL1-based therapy is a potential novel strategy to prevent colon cancer development.

Bacterial translocation and barrier dysfunction enhance colonic tumorigenesis

In the development of colon cancer, the intestinal dysbiosis and disruption of barrier function are common manifestations. In the current study, we hypothesized that host factors, e.g., vitamin D receptor deficiency or adenomatous polyposis coli (APC) mutation, contribute to the enhanced dysbiosis and disrupted barrier in the pathogenesis of colorectal cancer (CRC). Using the human CRC database, we found enhanced tumor-invading bacteria and reduced colonic VDR expression, which was correlated with a reduction of Claudin-10 mRNA and protein. In the colon of VDRΔIEC mice, deletion of intestinal epithelial VDR led to lower protein of tight junction protein Claudin-10. Lacking VDR and a reduction of Claudin-10 are associated with an increased number of tumors in the mice without myeloid VDR. Intestinal permeability was significantly increased in the mice with myeloid VDR conditional deletion. Further, mice with conditional colonic APC mutation showed reduced mucus layer, enhanced bacteria in tumors, and loss of Claudin-10. Our data from human samples and colon cancer models provided solid evidence- on the host factor regulation of bacterial translocation and dysfunction on barriers in colonic tumorigenesis. Studies on the host factor regulation of microbiome and barriers could be potentially applied to risk assessment, early detection, and prevention of colon cancer.

Formulation, characterization, pharmacokinetics and antioxidant activity evaluation of Pinus koraiensis nuts oil based coenzyme Q10 loaded nanoemulsion

Coenzyme Q10(CoQ10) is a well-known lipophilic antioxidant with good prospects for practical application of different fields including foods and pharmaceutics but has the drawback of low oral bioavailability because of its water insolubility and instability. Pinus koraiensis nut oil(PNO) is excellent in nutritional content and contains a great amount of unsaturated fatty acids that are helpful to the human body. It is easily oxidized, however, due to the high degree of unsaturation in its own structure, which limits its application. The present study aimed to formulate and characterize a CoQ10 loaded nanoemulsion based on PNO to overcome these problems of CoQ10 and PNO. Simultaneously, the physiological effects of the CoQ10 and PNO can work together in a synergistic way. In this study, coenzyme Q10 nanoemulsion(CoQ10-NE) with good stability was prepared by high pressure homogenization(HPH) technology. The CoQ10-NE was evaluated by TEM, FTIR, encapsulation rate, stability and release behavior in vitro. The bioavailability and the relationship between cellular oxidative stress and anticancer of CoQ10-NE was studied by pharmacokinetic and activity of malondialdehyde(MDA), superoxidedismutase(SOD) and glutathione peroxidase(GPx) about mouse colon cancer cells(CT26. WT). The area under the curve(AUC0-ꝏ) of CoQ10-NE was 3.25 folds higher than that of CoQ10 suspension, indicating that the bioavailability and absorption of CoQ10-NE are greatly increased. Also, at the same time, CoQ10-NE has a protective effect on CT26. WT cell damage induced by H2O2 compared with CoQ10 suspension and blank nanoemulsion. The final formulation solved the insolubility and instability of CoQ10 during use, along with providing a new technology for preparing CoQ10-NE with a long-term stability and good antioxidants in the prevention of colon cancer.

Effect of Lactobacillus fermentum ZS40 on the NF-κB signaling pathway in an azomethane-dextran sulfate sodium-induced colon cancer mouse model.

The occurrence of intestinal diseases such as colon cancer is closely related to the intestinal flora. Lactobacillus fermentum is a gut probiotic that plays an important role in chronic intestinal inflammation and colon cancer. In the current study, we investigated the effect of Lactobacillus fermentum ZS40 on NF-κB signaling pathway of azomethane-dextran sulfate sodium (AOM-DSS) -induced colon cancer in mice. Animals were divided into control group (NC), AOM-DSS-induced model group (CRC), AOM-DSS plus high-dose Lactobacillus fermentum ZS40 (ZS40-H), AOM-DSS plus low-dose Lactobacillus fermentum ZS40 (ZS40-L), AOM-DSS plus Lactobacillus bulgaricus (BLA), and AOM-DSS plus sulfasalazine (SD)-treated group. Observation of animal physiological activity (body weight and defecation), biochemical measurements, histopathological examination of colon tissue, qPCR to evaluate the expression of inflammation-related genes, immunohistochemical analysis of CD34 and CD117, and Western blot analysis of NF-κB signaling pathway were performed. Compared with the CRC group, the ZS40-H, ZS40-L, BLA, and SD groups had decreased levels of colon cancer marker proteins CD34 and CD117, and the number of abnormal colonic lesions observed by colon histology decreased, while the ZS40-H group showed excellent results. In addition, all probiotic interventions showed weight loss effects. The expression of inflammatory stimulators TNF-α and IL-1β in the probiotic treatment group decreased; the expression of key proteins IκBα and p65 in the NF-κB signaling pathway also decreased, resulting in a decrease in the expression of the target protein Cox-2. Therefore, administration of Lactobacillus fermentum ZS40 as a probiotic can alleviate intestinal inflammation and prevent colon cancer in mice.

Isomaltooligosaccharides inhibit early colorectal carcinogenesis in a 1,2-dimethylhydrazine-induced rat model.

Colon cancer (CC) is a multistage disease and one of the most common cancers worldwide. Establishing an effective treatment strategies of early colon cancer is of great significance for preventing its development and reducing mortality. The occurrence of colon cancer is closely related to changes in the intestinal flora structure. Therefore, remodelling the intestinal flora structure through prebiotics is a powerful approach for preventing and treating the occurrence and development of colon cancer. Isomaltooligosaccharides (IMOs) are often found in fermented foods and can directly reach the gut for use by microorganisms. In this study, a rat model of early colon cancer (DMH) was established by subcutaneous injection of 1,2-dimethylhydrazine, and the model rats were fed IMOs as a dietary intervention (DI). The untargeted faecal metabolomics, gut metabolome and intestinal function of the model rats were investigated. The results showed that DMH, DI and IMOs alone (IMOs) groups exhibited gut microbial community changes. In the DI group, there was an increased abundance of probiotics (Lactobacillus) and decreased abundance of CC marker bacteria (Fusobacterium). The key variations in the faecal metabolites of the DI group included decreased levels of glucose, bile acids (including deoxycholic acid and chenodeoxycholic acid) and amino acids (including L-glutamic acid and L-alanine). In addition, dietary intake of IMOs attenuated the intestinal inflammatory response, improved the intestinal microecological environment, and slowed the development of DMH-induced early CC in rats. This work provides a theoretical basis and technical support for the clinical prevention or treatment of CC with prebiotics.

Probiotic immunonutrition impacts on colon cancer immunotherapy and prevention.

The important role of the immune system in treating cancer has attracted the attention of researchers to the emergence of oncology research. Immunotherapy has shown that the immune system is important in the fight against cancer. The challenge has led researchers to analyze the impact of immunotherapy on improving the status of the immune system, modifying the resulting safety response, reducing toxicity, and improving the results. This study aimed to discuss the potential mechanisms of probiotics in preventing colon cancer. The mechanisms include the change in intestinal microbiota, the metabolic activity of microbiota, the binding and degradation of the carcinogenic compounds present in the lumen of the intestine, the production of compounds with anticancer activity, immune system modification, intestinal dysfunction, changes in host physiology, and inhibition of cell proliferation and induction of apoptosis in cancerous cells. By contrast, very few reports have shown the harmful effects of oral probiotic supplements. According to available evidence, further studies on probiotics are needed, especially in identifying bacterial species with anticancer potential, studying the survival of the strains after passing the digestive tract, reviewing potential side effects in people with a weak immune system, and ultimately consuming and repeating its use. This study emphasizes that the nutritional formula can modulate inflammatory and immune responses in cancer patients. This effect reduces acute toxicity, although the pathways and measurement of this immune response are unclear. Nutrition safety is an emerging field in oncology, and further research is required.

Ginger polysaccharide UGP1 suppressed human colon cancer growth via p53, Bax/Bcl-2, caspase-3 pathways and immunomodulation

In previous study, we got a purified ginger polysaccharide UGP1 and verified its significant antitumor activities on colon cancer HCT116 cells. In this article, we aimed to illustrate the underlying mechanism of UGP1 exerted antitumor activities on colon cancer by using in vitro cell models and in vivo animal models. The results demonstrated that UGP1 could induce S-phase cell cycle arrest, up-regulate the expression of Bax and p53, down-regulate the expression of Bcl-2, and activate the downstream protein caspase-9 and caspase-3, which was related to intrinsic apoptosis pathway on HCT116 cells. Moreover, UGP1 significantly stimulated RAW264.7 cell proliferation and secretion activity. Similarly, UGP1 inhibited tumor proliferation on tumor-bearing mice, increased the expression of p53 and the ratio of Bax/Bcl-2, enhanced the secretion of pro-inflammatory cytokines TNF-α, IL-2, IL-6 and decreased the secretion of pro-tumor cytokines TGF-β and bFGF in serum. In conclusion, it indicated that the UGP1 could suppress human colon cancer growth by inducing apoptosis via the regulation of p53, caspase-3, and Bax/Bcl-2 ratio-dependent pathway and regulating immune system activity. This investigation provided basic theoretical mechanism of ginger polysaccharide-exerted antitumor activities, and contributed to develop a possible functional food or adjuvant agent for prevention or treatment of colon cancer.

Changes of gut microbiota in colorectal cancer patients with Pentatrichomonas hominis infection.

Pentatrichomonas hominis is a parasitic trichomonads protozoa that parasitizes in the colon and cecum of humans and other animals. Our previous studies have demonstrated that infection with P. hominis is associated with the incidence of colon cancer (37.93%). However, the mechanism by which P. hominis infections increase the incidence of colon cancer remains unclear. Previous studies have suggested that certain parasites promote colon cancer by regulating gut microbiota. This study aimed to elucidate whether the association between P. hominis infections and the increased incidence of colon cancer is related to changes in gut microbiota. Therefore, the gut microbiota patients with colon cancer who were infected with P. hominis and uninfected patients with colon cancer were analyzed by 16S rRNA high-throughput sequencing. The results demonstrated that patients with colon cancer who were not infected with P. hominis showed increased gut bacterial diversity, a higher relative abundance of Alcaligenes sp., Leucobacter sp., Paraprevotella sp., Ruminococcaceae UCG-002, and a significant reduction in the abundance of Veillonella sp., compared to individuals without colon cancer. Additionally, the relative abundance of the Ruminococcaceae UCG-002 and the Eubacterium eligens groups was reduced, while the relative abundance of bacteria associated with colon cancer, including Flavonifractor sp., Lachnoclostridium sp., and the Ruminococcus gnavus group, increased significantly in patients with colon cancer who were infected with P. hominis, compared to those of uninfected patients with colon cancer. In conclusion, these results suggested that P. hominis infections may aggravate the development of colon cancer and the findings provide new insights for subsequent in-depth studies on the pathogenesis, diagnosis, and prevention of colon cancer.

Dietary Xenobiotics Derived from Food Processing: Association with Fecal Mutagenicity and Gut Mucosal Damage.

Whereas the mechanisms underlying the association of toxic dietary xenobiotics and cancer risk are not well established, it is plausible that dietary pattern may affect the colon environment by enhancing or reducing exposure to mutagens. This work aimed to investigate the association between xenobiotics intake and different stages of intestinal mucosal damage and colorectal cancer (CRC) screening and examine whether these associations may be mediated by altered intestinal mutagenicity. This was a case control study with 37 control subjects, 49 patients diagnosed with intestinal polyps, and 7 diagnosed with CRC. Lifestyle, dietary, and clinical information was registered after colonoscopy. For xenobiotics intake estimation the European Prospective Investigation into Cancer (EPIC) and the Computerized Heterocyclic Amines Resource for Research in Epidemiology of Disease (CHARRED) databases were used. The mutagenicity of fecal supernatants was assayed by the Ames test and light microscopy was used for the presence of aberrant crypt formation. Among all the potential carcinogens studied, the polyp group showed higher intakes of ethanol and dibenzo (a) anthracene (DiB(a)A). Besides, intakes between 0.75 and 1.29 µg/d of total polycyclic aromatic hydrocarbons (PAHs) were related with a higher risk of belonging to the polyp group. On the contrary, an intake of wholegrain cereals greater than 50 g/d was associated with a reduction in the relative risk of belonging to the polyp group. Heterocyclic amines (HAs) such as 2-amino-1-methyl-6-phenylimidazo (4,5,b) pyridine (PhIP) were associated with an increased level of mutagenicity in polyps. This study is of great interest for the identification of possible therapeutic targets for the early prevention of colon cancer through diet.

Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women’s Health Initiative

Proton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Women’s Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (n = 9186) nor risk of endometrial cancer (n = 1231). The risk of CRC (n = 2280) was significantly lower in PPI users (HR = 0.75, 95% CI = 0.61–0.92), but not in H2RA users (HR = 1.13, 95% CI = 0.97–1.31). The association of PPI use with CRC was apparent regardless of BMI or NSAID use, and was stronger with longer PPI duration (p = 0.006) and potency (p = 0.005). The findings that PPI use, but not H2RA use, demonstrate an inverse dose-response relationship with risk of CRC is consistent with preclinical data showing FASN inhibition prevents colon cancer progression and supports a role of PPI in CRC prevention.

Parecoxib expresses anti-metastasis effect through inhibition of epithelial-mesenchymal transition and the Wnt/β-catenin signaling pathway in human colon cancer DLD-1 cell line.

Colorectal cancer is the third leading cause of cancer death in Taiwan. Current treatments involve combination of surgical resection, radiation, and chemotherapy. These treatments have demonstrated to increased five-year survival of a patient with colorectal cancer. However, metastasis is a major capability of cancer cells that causes poor prognosis, recurrence, and even death. Epidemiological and clinical studies have suggested the use of non-steroidal anti-inflammatory drugs (NSAIDs) as an effective class of compounds to prevent colon cancer. Parecoxib is an NSAID and the only parenterally administered selective cyclooxygenase (COX)-2 inhibitor. In this study, we evaluated whether parecoxib inhibits the metastasis of DLD-1 human colon cancer cells, a COX-2 null cell line, and the underlying mechanism. Cell migration of the DLD-1 cells was significantly inhibited by parecoxib treatment as shown by the Transwell migration assay. This enhanced anti-migration effect was correlated with the attenuated phosphorylation of Akt, expression of vimentin (a mesenchymal marker), and β-catenin, and corresponded with the upregulated GSK3β and E-cadherin (an epithelial marker). These findings suggested that parecoxib could inhibit the epithelial-mesenchymal transition (EMT) and metastasis in human colon cancer cells by downregulating β-catenin. Thus, parecoxib could provide a novel prospective strategy for a combination treatment with chemotherapeutic drugs against metastasis of human colon cancer.