Role In Colon Cancer Prevention Research Articles

Lacticaseibacillus rhamnosus—A Promising Tool for Colorectal Cancer Treatment

Probiotic strains such as Lactobacillus spp. are already known for their beneficial effect on human health and new research supports their role in colon cancer prevention and treatment. The current study reports the effect of different concentrations of Lacticaseibacillus rhamnosus (LGG, 106–109 CFU/mL), alone or in association with 5-fluorouracil (5-FU, 10 μM), tested against normal HaCaT cells, HT-29 colorectal adenocarcinoma and HCT-116 colorectal carcinoma cell lines. The underlying cytotoxic effect was further investigated. LGG treatment of HT-29 and HCT-116 cells caused a variety of apoptotic-related nuclear morphological changes, as revealed by DAPI staining. ELISA studies showed that LGG treatment increased caspase-3 activity and pro-apoptotic BAX protein levels while decreasing anti-apoptotic Bcl-2 protein levels and the proto-oncogene Cyclin D1. A more detailed examination of the mitochondrial function revealed that high concentrations of LGG can impair mitochondrial function in HT-29 and HCT-116 cancer cells. All of these findings suggest that LGG has a pro-apoptotic, mitochondrial-targeted, cytotoxic effect on both colon cancer cell lines studied.

Effect of Saccharomyces Boulardii Cell Wall Extracts on Colon Cancer Prevention in Male F344 Rats Treated with 1,2-Dimethylhydrazine

ABSTRACTThe effect of Saccharomyces boulardii cell wall extracts on colon cancer prevention in rats treated with 1,2-dimethylhydrazine was investigated. A crude insoluble glucan (0.5 and 1.0 mg/kg/day) and a crude mannoprotein extract (0.3 and 3.0 mg/kg/day) were administered in rats by gavage for 12 weeks along with a high fat low fiber diet whereupon rats were sacrificed and aberrant crypt foci (ACF) were counted in the colon. Moreover, NAD(P)H: quinone reductase (QR) and harmful fecal enzymes (β-glucosidase and β-glucuronidase) were quantified in the liver and in the caecum, respectively. Results showed a reduction in ACF counts, a decreased β-glucuronidase activity and an increased QR activity when rats were treated only with insoluble glucan. While these enzymatic modulations may be constituted one of the mechanisms that is responsible for the reduction of ACF counts observed, the reduction of ACF counts caused by insoluble glucan should be addressed, at least, as a biomarker of their cancer-prevention properties. To our knowledge, this is the first study demonstrated that crude cell wall extract obtained from S. boulardii could have a potential role in colon cancer prevention in vivo by revealing the potential implication of QR and β-glucuronidase modulation.

Effects of a grape-supplemented diet on proliferation and Wnt signaling in the colonic mucosa are greatest for those over age 50 and with high arginine consumption.

A diet rich in fruits and vegetables, and a grape-derived compound, resveratrol, have been linked to a reduced incidence of colon cancer. In vitro and in vivo, resveratrol suppresses Wnt signaling, a pathway constitutively activated in over 85 % of colon cancers.Thirty participants were placed on a low resveratrol diet and subsequently allocated to one of three groups ingesting 1/3-to-1 lb (0.15–0.45 kg) of grapes per day for 2 weeks. Dietary information was collected via 24-h recall. Colon biopsies for biomarker analysis were obtained pre- and post-grape and evaluated for the expression of Wnt pathway target genes and for markers of proliferation by RT-PCR and immunohistochemistry.Participants lost an average of 2 · 6 lb (1.2 kg, p = 0 · 0018) during the period of grape ingestion. The expression of CyclinD1 (p < 0 · 01), AXIN2, CD133 (p = 0 · 02) and Ki67 (p = 0 · 002) were all reduced after grape ingestion. Individuals over 50 years of age and those with high dietary arginine consumption had increased basal expression of CyclinD1, AXIN2, cMYC and CD133 (p value range 0 · 04 to <0 · 001) that, following grape ingestion, were reduced to levels seen in younger participants.The reduction in Wnt signaling and mucosal proliferation seen following short-term ingestion of 1/3–1 lb (0.15–0.45 kg) of grapes per day may reduce the risk of mutational events that can facilitate colon carcinogenesis. The potential benefit is most marked for high-risk older individuals and individuals whose diet is high in arginine intake. Dietary grape supplementation may play a role in colon cancer prevention for high-risk individuals.

Emerging Evidence on the Role of Estrogenic Sorghum Flavonoids in Colon Cancer Prevention

Consumption of whole grains has been linked to reduced risk of colon cancer. The benefits of fiber and antioxidant minerals and vitamins found in whole grains are well recognized. The inherent estrogen-like activities of specific polyphenols contained in whole grains also play an important role in colon cancer prevention. Estrogen is believed to protect damaged colonocytes and prevent them from developing into malignancies. The protective effects of estrogen, such as induction of apoptosis and tumor-suppressing genes, are believed to be mediated via estrogen receptor-β, the predominant estrogen receptor (ER) in the colon. Emerging evidence on the role of specific flavonoids that are abundant in sorghum in ER-mediated colon cancer prevention are discussed. The overall implication of the evidence for the importance of whole grain consumption in colorectal cancer prevention is highlighted.

Methylselenol, a selenium metabolite, inhibits colon cancer cell growth and cancer xenografts in C57BL/6 mice (374.2)

Data indicate that methylselenol is a critical selenium (Se) metabolite for anticancer activity in vivo but its role in colon cancer prevention remains to be characterized. This study tested the hypothesis that methylselenol inhibits the growth of colon cancer cells and tumors. We found that submicromolar methylselenol exposure induced apoptosis and inhibited cell growth in cancerous colon HCT116 cells through a blockade of extracellular‐regulated kinase1/2 (ERK1/2) pathway, but to a much lesser extent in noncancerous NCM460 colon cells. Consistent with these in vitro observations, a daily single oral dose (0, 1 or 3 mg Se/kg body weight) of methylseleninic acid (MSeA), a methylselenol precursor, for 5 weeks inhibited colon tumor volume and tumor burden (weight) up to 61% when compared with control group, and this inhibition was associated with a reduction of plasma tumor necrosis factor (TNFα) level but high blood glutathione peroxidase (GPx) activities in C57BL/6 mice supplemented with MSeA. Furthermore, we also found that MSeA (1 mg/kg body wt) increased the activation of caspase‐3, a major apoptotic enzyme, in tumor tissues. Taken together, cancer cell specific inhibition, high blood GPx activities, caspase‐3 activities in tumor tissue and a reduction of plasma TNFα may be part of the underlying molecular basis for Se’s protective effect against colon tumor growth.

Mechanisms linking dietary fiber, gut microbiota and colon cancer prevention

Many epidemiological and experimental studies have suggested that dietary fiber plays an important role in colon cancer prevention. These findings may relate to the ability of fiber to reduce the contact time of carcinogens within the intestinal lumen and to promote healthy gut microbiota, which modifies the host's metabolism in various ways. Elucidation of the mechanisms by which dietary fiber-dependent changes in gut microbiota enhance bile acid deconjugation, produce short chain fatty acids, and modulate inflammatory bioactive substances can lead to a better understanding of the beneficial role of dietary fiber. This article reviews the current knowledge concerning the mechanisms via which dietary fiber protects against colon cancer.

Genistein: mechanisms of action in colorectal cancer

383 ISSN 1758-194X 10.2217/CRC.13.51 © 2013 Future Medicine Ltd Colorect. Cancer (2013) 2(5), 383–385 1Division of Hematology & Medical Oncology, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, 1 Gustave L Levy Place, Box 1128, New York, NY 10029, USA *Author for correspondence: Tel.: +1 212 659 5420; Fax: +1 212 659 5599; sofya.pintova@mountsinai.org With the advent of modern medicine and technology there has been great interest in understanding how natural substances that have been consumed for thousands of years affect the human physiology and molecular machinery. Environmental factors, most notably diet, are well known to influence a number of disease states including both metabolic syndromes and cardiovascular disorders. More recently, diet has been implicated in modulating the risk of cancer. The incidence of cancer varies among ethnic groups and even among individuals of the same ethnic group residing in different geographic regions when they consume a diet specific to that region. For example, Asian women who moved to the USA were found to ingest higher amounts of tofu than Asian–American women born in the USA [1], and US-born Japanese migrants have a significantly higher incidence of colorectal cancer compared with their foreign-born counterparts [2]. It has been suggested that populations consuming a soy-rich diet may have a lower risk of specific malignancies and extracts of soy have been investigated for the prevention and treatment of neoplasia. One of such extracts, genistein, was first isolated from a plant Genista tinctoria in 1899 and chemically synthesized in the 1920s. It is a plant-derived isoflavone and phytoestrogen found predominantly in soy products that has been studied for a potential role in colon cancer prevention and treatment.

Abstract 198: Resveratrol's Metabolomic biomarkers of efficacy: the missing link to chemoprevention.

Abstract Chemoprevention has received considerable attention over the last decade. The notion of using bioactive food components to reduce the risk of developing, or the recurrence of cancer has long been recognized. Resveratrol (a naturally occurring polyphenolic compound) has been studied extensively with considerable evidence demonstrating its efficacy as an anti-inflammatory and anti-cancer agent, with the most evidence for its role in colon cancer prevention. However, Resveratrol intervention studies in clinical trials still remains controversial, due to the lack of biomarkers of efficacy. Utilizing Metabolomic analysis we have identified biomarkers of efficacy in a pre-clinical model of inflammation-induced colorectal carcinogenesis. Metabolomics is the process of identifying metabolites present in biological specimens. Our study has demonstrated the chemopreventative activity of Resveratrol in mice treated with the chemical carcinogen azoxymethane (AOM) and then exposed to colonic irritant dextran sodium sulfate (DSS) to induce inflammation-associated colon carcinogenesis. We found a diet enriched in Resveratrol resulted in a reduction in tumor incidence in AOM/DSS treated mice by 29 percent. Furthermore, we identified several biomarkers that are indicative of Resveratrol chemopreventive activities. Prior studies have shown Resveratrol's role in inhibiting several key enzymes important during the carcinogenesis process. We have correlated such findings with Metabolomic biomarkers. We found a significant reduction in Arachidonic acid, the limiting reagent of pro-inflammatory enzyme COX-2, and a reduction in spermidine a product of Ornithine decarboxylase, an enzyme that promotes proliferation. More intriguingly, we found biomarkers representing changes in bile acids by Resveratrol, which highlight chemopreventative activities that were not previously described. We found that Resveratrol treatment causes a reduction in tumorigenic secondary bile acids, deoxycholic acid and lithocholic acid, which are metabolic byproducts of intestinal bacteria. These data suggested that dietary supplementation with Resveratrol results in a healthy microbiome. These pre-clinical studies should easily be translated into clinical studies designed to ascertain chemopreventive efficacy for bioactive compounds like Resveratrol, all with the objective to identify patients that will benefit from an intervention. Citation Format: Shakir Saud, Matthew Young, Ed Karoly, Chris Bernard, Nancy Colburn, Young Kim. Resveratrol's Metabolomic biomarkers of efficacy: the missing link to chemoprevention. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 198. doi:10.1158/1538-7445.AM2013-198

Methylselenol, a selenium metabolite, inhibits colon cancer cell growth in vitro and in vivo

Methylselenol is hypothesized to be a critical selenium (Se) metabolite for certain anticancer activities in vivo but its role in colon cancer prevention remains to be characterized. This study tested the hypothesis that methylselenol inhibits the growth of colon cancer cells and tumors. We found that submicromolar methylselenol exposure inhibited cell growth and led to an increase in the G1 and G2 fractions with a concomitant drop in the S‐phase, and an induction of apoptosis in cancerous colon HCT116 cells, but to a much lesser extent in noncancerous NCM460 colon cells. Furthermore, in agreement with the fact that blockade of extracellular‐regulated kinase1/2 (ERK1/2) and p38 mitogen activated protein kinase (p38 MAPK) pathways suppresses the growth of colon tumors, we demonstrated that methylselenol inhibited ERK1/2 and p38 MAPK in cancerous colon HCT116 cells but also to a lesser extent in NCM460 cells. Consistent with these in vitro observations, a daily single oral dose (1 to 3 mg Se/kg body weight) of methylseleninic acid, a methylselenol precursor, for 5 weeks inhibits the growth of colon cancer xenografts in a C57/BL mouse model. Taken together, methylselenol's strong potential of inhibiting colon cancer cell proliferation, may be an important mechanism by which Se exerts its anticancer activity in colon cancer prevention.

The anticarcinogenic potential of essential oil and aqueous infusion from caper (Capparis spinosa L.)

The present study assessed the influence of essential oil and aqueous infusion from wild-grown caper (Capparis spinosa L.) on cell growth, NF-κB activation, apoptosis and cell cycle in the human colon carcinoma cell line, HT-29. Methyl isothiocyanate (92.06%), a degradation product of glucosinolate glucocapparin, was detected as major component of essential oil from caper leaves and flower buds. Aqueous infusion of caper showed an interesting and variegate compositional pattern containing several phenolic compounds, among which a flavonol glycoside, rutin (quercetin 3-O-rutinoside, 50.7%) and 5-caffeoyl-quinic acid (chlorogenic acid, 17.5%) were detected as dominant. Caper essential oil and aqueous infusion showed time- and dose-dependent high inhibitory effect on HT-29 cell proliferation. In addition, they induced the inhibition on nuclear factor κB (NF-κB) activity in a dose-dependent manner, while they did not show any effect on apoptosis in HT-29 cells. Flow cytometric analysis indicated that treatment with caper essential oil and aqueous infusion resulted in G2/M cell cycle arrest in a dose-dependent manner. Presented results suggest that caper contains volatile and non-volatile compounds which potentially can play an important role in colon cancer prevention.

Impact of Polyphenol Metabolites Produced by Colonic Microbiota on Expression of COX-2 and GSTT2 in Human Colon Cells (LT97)

Polyphenols may play an important role in colon cancer prevention. After entering the colon, they are subjected to metabolism by the human gut microbiota. The objective of the present study was to analyze the impact of selected intestinal metabolites on modulation of enzymes involved in detoxification and inflammation in human adenoma cells LT97. LT97 cells were incubated with 3,4-dihydroxyphenylacetic acid (ES) and 3-(3,4-dihydroxyphenyl)-propionic acid (PS), metabolites of quercetin and chlorogenic acid/caffeic acid, respectively. The effect on cell number was analyzed using 4'- 6-diamino-2-phenylindole-dihydrochloride (DAPI)-staining. Modulation of glutathione S-transferase T2 (GSTT2) and cyclooxygenase-2 (COX-2) was measured by real-time PCR and Western blot. Comet assay was performed to assess the impact on DNA damage caused by the GSTT2 substrate cumene hydroperoxide (CumOOH). Polyphenol metabolites did not affect cell number but significantly upregulated GSTT2 expression and decreased COX-2. The latter was confirmed via Western blot. CumOOH-induced DNA damage was significantly reduced compared to the control. An upregulation of GSTT2 and downregulation of COX-2 could possibly contribute to the chemopreventive potential of polyphenols after degradation in the gut. Working with polyphenol metabolites is an important prerequisite to better understand the in vivo effects of pure polyphenols.

Physical activity and risk of colon adenoma: a meta-analysis

Background:Little evidence is available on the relation of physical activity with colon adenomas, a colon cancer precursor.Methods:We conducted a systematic literature review and meta-analysis of published studies (in English) through April 2010, examining physical activity or exercise and risk or prevalence of colon adenoma or polyp. Random effects models were used to estimate relative risks (RRs) and corresponding confidence intervals (CIs). A total of 20 studies were identified that examined the association and provided RRs and corresponding 95% CIs.Results:A significant inverse association between physical activity and colon adenomas was found with an overall RR of 0.84 (CI: 0.77–0.92). The association was similar in men (RR=0.81, CI: 0.67–0.98) and women (RR=0.87, CI: 0.74–1.02). The association appeared slightly stronger in large/advanced polyps (RR=0.70, CI: 0.56–0.88).Conclusion:This study confirms previous reports of a significant inverse association of physical activity and colon adenoma, and suggests that physical activity can have an important role in colon cancer prevention.

Regression of Follicular Lymphoma With Devil’s Claw: Coincidence or Causation?

Cancer patients frequently use alternative therapies. Two follicular lymphoma patients who had objective tumour regression after taking Devil's Claw without cytotoxic therapy are reported here. Patient 1 presented with coexistent immunoglobulin G plasma cell dyscrasia and stage iiia lymphoma (nodes 5 cm in diameter). Computed tomography scan 10 months later showed partial regression. On enquiry, it was learned that the patient was taking Devil's Claw and Essiac (Essiac Products Services, Pompano Beach, FL, U.S.A.). This patient later developed overt myeloma, at which time he stopped the herbal supplements and underwent high-dose chemotherapy and stem cell transplantation, since which no lymphoma progression has occurred. Patient 2 presented with stage IIIA lymphoma (nodes 2.5 cm in diameter). He learned of patient 1 through our lymphoma patient support group and started Devil's Claw. Computed tomography scan 11 months later showed decreased adenopathy and splenomegaly, which has been sustained for 4 years. Devil's Claw tuberous root has anti-inflammatory properties, probably through suppression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase expression. There are no prior reports of anticancer activity. Inhibition of COX-2 has a role in colon cancer prevention, has been implicated in lymphomagenesis, and is associated both with lymphoma stage and with response to treatment. However, spontaneous regression in lymphoma has been reported in 16% of patients in one series, of whom none were on herbal medications or COX-2 inhibitors. The key issue in both these patients is whether disease regression was "spontaneous" or causally related to therapy with Devil's Claw. The timing of the response suggests a positive effect. Further investigation is warranted, preferably with a COX-2 inhibitor of known purity.

Cranberry extract and quercetin modulate the expression of cyclooxygenase‐2 (COX‐2) and IκBα in human colon cancer cells

AbstractBACKGROUND: Cranberry (Vaccinium marcocarpon) fruit and quercetin, a major flavonoid found in cranberries, are likely contributors to chemoprevention, and their anti‐inflammatory activities may play a potential role in colon cancer prevention. The aim of this study was to examine the effect of cranberry extract and quercetin on basal expression of cyclooxygenase‐2 (COX‐2) and IκBα as well as the effect on phorbol 12‐myristate 13‐acetate (PMA)‐induced COX‐2 expression in colon cancer cells.RESULTS: HT‐29 human colon adenocarcinoma cells were treated with various concentrations of cranberry extract or quercetin and/or PMA, and the protein expression of COX‐2 and IκBα was determined. The results indicated that cranberry extract and quercetin decreased COX‐2 expression and suppressed degradation of IκBα in unstimulated cells. In PMA‐stimulated cells, cranberry extract was also able to decrease COX‐2 expression and suppress degradation of IκBα.CONCLUSION: The results suggest that a possible mechanism involved in the anti‐cancer activity of cranberry and quercetin is partly mediated through its anti‐inflammatory action. These findings indicate that cranberry and quercetin may reduce the risk of colon cancer possibly by suppressing inflammatory responses. Copyright © 2008 Society of Chemical Industry

Cell kinetics and gene expression changes in colorectal cancer patients given resistant starch: a randomised controlled trial

Objective: This study investigated the effects of oral supplementation of resistant starch (RS) on tumour cell and colonic mucosal cell kinetics and on gene expression in patients with colorectal cancer...

Awareness of the role of physical activity in colon cancer prevention

Objective This study examined the prevalence and correlates of U.S. adults’ awareness of the role that physical activity plays in preventing colon cancer. Methods Data were analyzed for 1932 respondents to the Health Information National Trends Survey who answered a question about factors that reduce the chances of getting colon cancer. Individuals who listed physical activity in response to this question were denoted as being aware of its role in colon cancer prevention. Results Few respondents (15.0%) listed physical activity as a means of reducing colon cancer risk. Awareness was especially low among individuals aged 50 years and over, those with lower levels of education, individuals who believe that physical activity recommendations are confusing, those reporting less exposure to information about physical activity and cancer, individuals who did not report looking for information about cancer, those with poorer knowledge of colon cancer symptoms, and less physically active individuals. Conclusions There is poor awareness among U.S. adults of the role that physical activity plays in preventing colon cancer. Practice implications Health care providers should routinely inform their patients that engaging in regular physical activity greatly reduces the risk of developing colon cancer.

Potential Role of Flavonoids in the Prevention of Intestinal Neoplasia: A Review of Their Mode of Action and Their Clinical Perspectives

Intestinal neoplasia (adenomas and carcinomas) can possibly be prevented by a diet rich in vegetables and fruits, treatment with aspirin and other nonsteroidal antiinflammatory drugs, and early colonoscopic removal of adenomas. Ballast, fiber, and secondary plant products could play a major role in colon cancer prevention. Recently there has been much experimental work in vitro and in vivo about flavonoids as inducers of bioprevention. Flavonoids are secondary plant products with a wide variety of beneficial biological properties, and they possess anticarcinogenic, antimutagenic, and antioxidative modes of actions. Flavonoids are the main components of a healthy diet containing fruits and vegetables and are concentrated especially in tea, apples, and onions. We will focus this review on flavonoids which are derived from tea products such as proanthocyanidins (green tea) and flavons (camomille tea). Oral supplementation with bioflavonoids derived from tea could be used in humans to prevent growth of intestinal neoplasia such as adenomatous polyps of the colon. Flavonoids are a large group of natural compounds of which only a few have been used in animal models, cell cultures, and enzyme studies to inhibit mutagenic and carcinogenic events. Their clinical mode of action was evaluated by epidemiological studies, but no intervention studies in humans have been performed so far. In vitro flavonoids can bind electrophils, inactivate oxygen radicals, prevent lipid peroxidation, and inhibit DNA oxidation. In cell cultures they increase the rate of apoptosis, inhibit cell proliferation, and angiogenesis. In vivo they can induce the activities of protective enzymes (conjugating enzymes such as glutathione transferases and glucuronosyl transferases) of the intestine and the liver. In models of intestinal polyposis, flavonoids suppress polyp formation. Some epidemiological studies show a protective effect of flavonoids contained in fruits, vegetables, and tea. Flavonoid mixtures of tea origin supplied as nutritional supplements could be studied as a new way of bioprevention of intestinal neoplasia (colon adenomas and cancer). Therefore, a controlled, randomized clinical study should be performed to evaluate the efficacy of flavonoids.

NO-donating nonsteroidal antiinflammatory drugs (NSAIDs) inhibit colon cancer cell growth more potently than traditional NSAIDs: a general pharmacological property?

The novel nitric oxide-donating nonsteroidal antiinflammatory drugs (NO-NSAIDs), consisting of a traditional NSAID to which a NO releasing moiety is covalently attached, may have an important role in colon cancer prevention and/or treatment. Preclinical studies have shown that NO-aspirin (NO-ASA) is more potent than traditional ASA in preventing colon cancer. Preclinical and clinical studies have also documented its superior safety, compared to traditional ASA. To evaluate the role of this structural modification on the cancer cell growth inhibitory effect of NSAIDs, we studied seven pairs of traditional NSAIDs (ASA, salicylic acid, indomethacin, sulindac, ibuprofen, flurbiprofen, piroxicam) and their corresponding NO-NSAIDs. All NO-NSAIDs (except NO-piroxicam which is a salt and not a true NO-NSAID) have greater potency in inhibiting HT-29 and HCT-15 colon cancer cell growth compared to their NSAID counterparts: the IC 50s of the NO-NSAIDs were enhanced between 7- and 689-fold in HT-29 cells and 1.7- to 1083-fold in HCT-15 cells over those of the corresponding NSAIDs. Their growth inhibitory effect is due to a profound cell kinetic effect consisting of reduced cell proliferation and enhanced cell death. Since HT-29 cells express cyclooxygenases but HCT-15 do not, this effect appears independent of cyclooxygenase in the colon cancer cells. Thus the structural modification of these traditional NSAIDs leading to NO-NSAIDs enhances their potency in inhibiting colon cancer cell growth. Our findings suggest that the enhanced potency imparted on NSAIDs by this structural modification represents a pharmacological property that may be a general one for this class of compounds.

Resistant Starches and Health

It was initially hypothesized that resistant starches, i.e., starch that enters the colon, would have protective effects on chronic colonic diseases, including reduction of colon cancer risk and in the treatment of ulcerative colitis. Recent studies have confirmed the ability of resistant starch to increase fecal bulk, increase the molar ratio of butyrate in relation to other short-chain fatty acids, and dilute fecal bile acids. However the ability of resistant starch to reduce luminal concentrations of compounds that are damaging to the colonic mucosa, including fecal ammonia, phenols, and N-nitroso compounds, still requires clear demonstration. As such, the effectiveness of resistant starch in preventing or treating colonic diseases remains to be assessed. Nevertheless, there is a fraction of what has been termed resistant (RS1) starch, which enters the colon and acts as slowly digested or lente carbohydrate in the small intestine. Foods in this class are low glycemic index and have been shown to reduce the risk of chronic disease. They have been associated with systemic physiological effects such as reduced postprandial insulin levels and higher HDL cholesterol levels. Consumption of low glycemic index foods has been shown to be related to reductions in risk of coronary heart disease and Type 2 diabetes. Type 2 diabetes has in turn been related to a higher risk of colon cancer. If carbohydrates have a protective role in colon cancer prevention this may lie partly in the systemic effects of low glycemic index foods. The colonic advantages of different carbohydrates, varying in their glycemic index and resistant starch content, therefore, remain to be determined. However, as recent positive research findings continue to mount, there is reason for optimism over the possible health advantages of those resistant starches, which are slowly digested in the small intestine.

Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

BackgroundCurcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an anti-oxidant and it can act as an anti-inflammatory agent. The aim of this study was to elucidate mechanisms and effect of curcumin in colon cancer cells using gene expression profiling.MethodsGene expression changes in response to curcumin exposure were studied in two human colon cancer cell lines, using cDNA microarrays with four thousand human genes. HT29 cells were exposed to two different concentrations of curcumin and gene expression changes were followed in time (3, 6, 12, 24 and 48 hours). Gene expression changes after short-term exposure (3 or 6 hours) to curcumin were also studied in a second cell type, Caco-2 cells.ResultsGene expression changes (>1.5-fold) were found at all time points. HT29 cells were more sensitive to curcumin than Caco-2 cells. Early response genes were involved in cell cycle, signal transduction, DNA repair, gene transcription, cell adhesion and xenobiotic metabolism. In HT29 cells curcumin modulated a number of cell cycle genes of which several have a role in transition through the G2/M phase. This corresponded to a cell cycle arrest in the G2/M phase as was observed by flow cytometry. Functional groups with a similar expression profile included genes involved in phase-II metabolism that were induced by curcumin after 12 and 24 hours. Expression of some cytochrome P450 genes was downregulated by curcumin in HT29 and Caco-2 cells. In addition, curcumin affected expression of metallothionein genes, tubulin genes, p53 and other genes involved in colon carcinogenesis.ConclusionsThis study has extended knowledge on pathways or processes already reported to be affected by curcumin (cell cycle arrest, phase-II genes). Moreover, potential new leads to genes and pathways that could play a role in colon cancer prevention by curcumin were identified.