tannins and Colonic-Neoplasms

Topics: Animals; Breast Neoplasms; Carcinogens, Environmental; Colonic Neoplasms; Diet; Dietary Fats; Esophageal Neoplasms; Humans; Liver Neoplasms; Lung Neoplasms; Mammary Neoplasms, Experimental; Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Tannins; Urinary Bladder Neoplasms

Colon cancer was the second leading cause of cancer-related death in 2019. We herein investigated the effects of acertannin containing Acer species on azoxymethane (AOM)/dextran sulfate sodium (DDS)-induced colon cancer growth and changes in the colonic levels of interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1, IL-10, and programmed cell death-1 (PD-1). Colorectal carcinogenesis was induced by an intraperitoneal injection of AOM (10 mg/kg) on days 0 and 27. Mice were given 1% (w/v) DSS drinking water ad libitum on days 7-14, 32-33, and 35-38. Acertannin (30 and 100 mg/kg) was orally administered on days 1-16, discontinued for 11 days (days 16-26), and then administered again on days 27-41. The colonic levels of cytokines, a chemokine, and PD-1 were measured using the respective ELISA kits. The number and area of tumors in mice treated with acertannin (100 mg/kg) decreased by 53.9 and 63.1%, respectively. Furthermore, the colonic levels of IL-1β, MCP-1, IL-10, and PD-1 showed reductions of 57.3, 62.9, 62.8, and 100%, respectively, while the numbers of cyclooxygenase-2 (COX-2)-, thymocyte selection-associated high mobility group box proteins (TOX)/TOX2-, PD-1-, and signal transducer and activator of transcription 3 (STAT3) phosphorylation-positive numbers decreased by 79.6, 77.9, 93.8, and 100%, respectively. In conclusion, the inhibitory effects of acertannin on AOM/DSS-induced colon tumor growth appear to be associated with reductions in the colonic levels of IL-1β, MCP-1, IL-10, and PD-1 through the down-regulated expression of COX-2 and TOX/TOX2 in the tumor microenvironment.

Topics: Animals; Azoxymethane; Chemokine CCL2; Colon; Colonic Neoplasms; Cyclooxygenase 2; Dextran Sulfate; Interleukin-10; Interleukin-1beta; Mice; Mice, Inbred C57BL; Programmed Cell Death 1 Receptor; Tannins; Tumor Microenvironment

Triple-negative breast cancer (TNBC) and colon cancer (CC) are two stigmatic examples of poorly treatable tumors, whose progression critically depends upon hyperactivation of the Wnt signaling. Development of specific anti-Wnt inhibitors is required to develop drugs against these and other Wnt-dependent cancers. Natural products, especially plants, have been used for the treatment of various diseases from ancient times. We examined extracts from several indigenous Cameroonian herbs and tested their effects on proliferation and Wnt signaling in TNBC and CC cells. Extracts from "fruit rouge", Syzygium guineense Wall. (Myrtaceae), demonstrated a strong activity against these cancer cells, as well as CC organoids. We found TNBC cells to significantly upregulate expression of Wnt3a, and the effects of S. guineense extracts on TNBC cell proliferation correlated with inhibition of the Wnt3a-induced β-catenin stabilization and transcriptional response. HPLC analysis revealed that the active components belong to tannins. We found a direct destabilizing effect of S. guineense extract on Wnt3a and other Wnt proteins, identifying a novel mechanism of action of tannins on the Wnt signaling pathway and cancer cell proliferation. Being edible, this African plant may have an important cancer-preventive nutritional value.

Topics: Cameroon; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colonic Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Plant Extracts; Syzygium; Tannins; Triple Negative Breast Neoplasms; Wnt Proteins; Wnt Signaling Pathway; Wnt3A Protein

Tannic acid (TA), a naturally occurring polyphenolic acid that is primarily found in grapes and green tea, exhibits potent antioxidant and anticarcinogenic characteristics. However, the underlying molecular mechanisms and targets of TA, which are responsible for cancer prevention, remain elusive. In the present study, we used TA-functionalized magnetite nanoparticles to identify pyruvate kinase isoenzyme M2 (PKM2) as the direct target of TA. We report that TA selectively inhibits the pyruvate kinase activity of PKM2, rather than protein kinase activity and PKM2 expression, to suppress colorectal cancer (CRC) cell proliferation. Furthermore, we had discovered that lysine residue 433 (K433) is a selective druggable site. Through direct binding to lysine residue 433, TA triggers the dissociation of PKM2 tetramers and further blocks the metabolic activity of PKM2. Notably, TA has no effect on PKM1 activity as TA does not bind to it. Taken together, these findings show that TA is worthy of consideration as a promising PKM2 inhibitor for the prevention of CRC.

Topics: Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; HCT116 Cells; Humans; Isoenzymes; Phosphorylation; Pyruvate Kinase; Tannins

Calcium, phytic acid, polyphenols and fiber are major inhibitors of iron absorption and they could be found in excess in some diets, thereby altering or modifying the iron nutrition status. The purpose of this study is to evaluate the effect of calcium, tannic acid, phytic acid, and pectin over iron uptake, using an in vitro model of epithelial cells (Caco-2 cell line). Caco-2 cells were incubated with iron (10-30 μM) with or without CaCl2 (500 and 1,000 μM) for 24 h. Then, cells were challenged with phytic acid (50-150 μM); pectin (50-150 nM) or tannic acid (100-500 μM) for another 24 h. Finally, (55)Fe (10 μM) uptake was determined. Iron dialyzability was studied using an in vitro digestion method. Iron uptake in cells pre-incubated with 20 and 30 μM Fe was inhibited by CaCl2 (500 μM). Iron uptake decreased in cells cultured with tannic acid (300 μM) and CaCl2 (500-1,000 μM) (two-way ANOVA, p = 0.002). Phytic acid also decreased iron uptake mainly when cells were treated with CaCl2 (1,000 μM) (two-way ANOVA; p < 0.05). Pectin slightly decreased iron uptake (p = NS). Iron dialyzability decreased when iron was mixed with CaCl2 and phytic or tannic acid (T test p < 0.0001, for both) but not when mixed with pectin. Phytic acid combined with calcium is a strong iron uptake inhibitor. Pectin slightly decreased iron uptake with or without calcium. Tannic acid showed an unexpected behavior, inducing an increase on iron uptake, despite its low Fe dialyzability.

Topics: Adenocarcinoma; Analysis of Variance; Caco-2 Cells; Calcium; Calcium Chloride; Colonic Neoplasms; Dose-Response Relationship, Drug; Humans; Intestinal Absorption; Iron; Models, Biological; Pectins; Phytic Acid; Tannins

The influence of flaxseed (Linum usitatissimum L.) and its total non-digestible fraction (TNDF) on the expression of genes involved in azoxymethane (AOM)-induced colon cancer in Sprague Dawley rats was analyzed. The dose used in the animal model was two tablespoons of flaxseed per day, which is the dose recommended for humans. Flaxseed significantly decreased the crypt multiplicity (10.50 ± 3.5) compared with the AOM treatment (34.00 ± 11.0), which suggests that flaxseed exhibits a preventive effect against colon cancer. Both treatments (flaxseed and TNDF) influence the overexpression of genes involved in cell cycle arrest and mitochondrial apoptosis: p53, p21, bcl-2, bax and caspase-3. Flaxseed induced the expression of p53 and p21, whereas TNDF triggered the p21-independent expression of p53. This finding suggests that both of these treatments induced cell cycle arrest. In addition, TNDF induced mitochondrial apoptosis because the TNDF + AOM group exhibited the expression of caspase-3, decreased bcl-2 expression and increased bax expression. These results suggest that the expression of the analyzed genes is associated with the presence of dietary antioxidants linked to the cell wall of flaxseed.

Topics: Animals; Antioxidants; Apoptosis; Azoxymethane; Carcinogens; Cell Cycle Checkpoints; Colon; Colonic Neoplasms; Diet; Digestion; Flavonoids; Flax; Gene Expression; Male; Phenols; Phytotherapy; Rats; Rats, Sprague-Dawley; Seeds; Tannins

Currently, natural products have been shown to present interesting biological and pharmacological activities and are used as chemotherapeutic agents. Plants have historically been used in treating cancer and are recognized for their ability to produce secondary metabolites. Juglans regia L. (Juglandaceae) has medicinal applications to treat a wide range of diseases such as cancer.. The current study was designed to evaluate the antiproliferative activity of total extract as well as several fractions from the leaves of J. regia.The total phenolics, flavonoids, and condensed tannins content of these extracts were also determined to obtain further information on the correlation between the contents of phenolic compounds and antiproliferative effects as well as the leaf developmental stages.. Antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry methods against human oral cancer, breast adenocarcinoma and colon adenocarcinoma cell lines. The total phenolics, flavonoids, and condensed tannins were determined by Folin-Ciocalteu, aluminum chloride and butanol-HCl colorimetric methods.. Our present study has shown that chloroform fraction has the lowest IC(50) values (0.36-0.81 mg/mL) and also induces cell cycle arrest (G0\\G1 phase) after a 24 h treatment. The colorimetric methods showed the highest amount of total phenolics, flavonoids, and condensed tannins in the methanol fraction (120.28 ± 2.32, 59.44 ± 0.87, 227.00 ± 4.91 mg/g of dry weight of extract).. The results obtained herein indicate that walnut chloroform fraction may contain effective compounds which can be used as a chemotherapeutic agent.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Female; Flavonoids; Flow Cytometry; Humans; Inhibitory Concentration 50; Juglans; Mice; Mouth Neoplasms; NIH 3T3 Cells; Phenols; Plant Extracts; Plant Leaves; Tannins

Colon cancer is the third most common malignant neoplasm in the world and it remains an important cause of death, especially in western countries. The toxic environmental pollutant, 1, 2-dimethylhydrazine (DMH), is also a colon-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemically induced toxicity and also carcinogenesis. In the present study, we evaluated the chemopreventive efficacy of TA against DMH induced colon toxicity in a rat model. Efficacy of TA against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, histopathological changes and expression of early molecular markers of inflammation and tumor promotion. DMH treatment induced oxidative stress enzymes (p<0.001) and an early inflammatory and tumor promotion response in the colons of Wistar rats. TA treatment prevented deteriorative effects induced by DMH through a protective mechanism that involved reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression levels and TNF-α(p<0.001) release. It could be concluded from our results that TA markedly protects against chemically induced colon toxicity and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.

Topics: 1,2-Dimethylhydrazine; Animals; Anticarcinogenic Agents; Antioxidants; Catalase; Colitis; Colon; Colonic Neoplasms; Cyclooxygenase 2; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Male; Malondialdehyde; Nitric Oxide Synthase Type II; Oxidative Stress; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar; Superoxide Dismutase; Tannins; Tumor Necrosis Factor-alpha

Blechnum orientale Linn. (Blechnaceae) is used ethnomedicinally for the treatment of various skin diseases, stomach pain, urinary bladder complaints and sterilization of women. The aim of the study was to evaluate antioxidant, anticancer and antibacterial activity of five solvent fractions obtained from the methanol extract of the leaves of Blechnum orientale Linn.. Five solvent fractions were obtained from the methanol extract of B. orientale through successive partitioning with petroleum ether, chloroform, ethyl acetate, butanol and water. Total phenolic content was assessed using Folin-Ciocalteu's method. The antioxidant activity was determined by measuring the scavenging activity of DPPH radicals. Cytotoxic activity was tested against four cancer cell lines and a non-malignant cell using MTT assay. Antibacterial activity was assessed using the disc diffusion and broth microdilution assays. Standard phytochemical screening tests for saponins, tannins, terpenoids, flavonoids and alkaloids were also conducted.. The ethyl acetate, butanol and water fractions possessed strong radical scavenging activity (IC50 8.6-13.0 microg/ml) and cytotoxic activity towards human colon cancer cell HT-29 (IC50 27.5-42.8 microg/ml). The three extracts were also effective against all Gram-positive bacteria tested: Bacillus cereus, Micrococcus luteus, methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and Stapylococcus epidermidis(minimum inhibitory concentration MIC 15.6-250 mug/ml; minimum bactericidal concentration MBC 15.6-250 microg/ml). Phytochemical analysis revealed the presence of flavonoids, terpenoids and tannins. Ethyl acetate and butanol fractions showed highest total phenolic content (675-804 mg gallic acid equivalent/g).. The results indicate that this fern is a potential candidate to be used as an antioxidant agent, for colon cancer therapy and for treatment of MRSA infections and other MSSA/Gram-positive bacterial infectious diseases.

Topics: Adenocarcinoma; Anti-Bacterial Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Biphenyl Compounds; Cell Line; Cell Line, Tumor; Colonic Neoplasms; Ferns; Flavonoids; Free Radical Scavengers; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Neoplasms; Phenols; Picrates; Plant Leaves; Tannins; Terpenes

Cancer chemopreventive agents are designed to reduce the incidence of tumorigenesis by intervening at one or more stages of carcinogenesis. This study aimed to determine the effects of resveratrol (RES) and tannic acid (TA), which are chemopreventive agents, on the nitric oxide synthase (NOS) levels that are effective for development of cancer in colon and breast cancer cell lines. The CaCo-2 (human colon carcinoma cell line) and MCF-7 (Michigan Cancer Foundation-7; human breast adenocarcinoma cell line) cells were grown in the laboratory. RES and TA were used to treat CaCo-2 and MCF-7 cells. Nitric Oxide Synthase Assay Kit was used to determine the NOS enzyme activity of CaCo-2 and MCF-7. Statistical differences between control and RES- and TA-treated cells were calculated using the Student's t-test for double comparison. It was observed that NO activity was generally decreased in CaCo-2 and MCF-7 cells, in which RES and TA were applied. Results suggest that the phenolic compounds RES and TA have different effects on NOS enzyme activity of the colon and breast cancer cells.

Topics: Adenocarcinoma; Anticarcinogenic Agents; Breast Neoplasms; Caco-2 Cells; Cell Line, Tumor; Chemoprevention; Colonic Neoplasms; Female; Humans; Nitric Oxide Synthase; Phenols; Resveratrol; Stilbenes; Tannins

To investigate the effects of resveratrol and tannic acid on apoptosis, and Bcl-2 homologous antagonist/killer (Bak) and fas associated death domain (FADD) proteins in the CaCo-2 cell line.. In the present study, resveratrol and tannic acid were administrated in the CaCo-2 cell line at doses of 25, 50, and 100 microM. The CaCo-2 cells were grown and cultured in the Medical Biology Department, Eskisehir Osmangazi University, Eskisehir, Turkey in 2007. The effects of these agents on apoptotic index were determined by Apop Taq peroxidase kit and their effects on the ratios of Bak and FADD proteins by the immunohistochemical staining method at 24, 48, and 72 hours. Stained and non-stained cells in 30 separate areas of the 3 separate chamber slides, prepared for each group, were counted. The percentage of apoptosis, and Bak and FADD proteins was calculated with the control. Mean +/- standard error values were calculated for the 3 experiments.. Apoptotic index, Bak protein percentage ratio, and FADD protein percentage ratio values in all groups that received tannic acid and resveratrol increased when compared within the groups. This increase was found to be time and dose independent in all parameters.. Cells undergo apoptosis in 2 pathways (mitochondrial and death receptor) in resveratrol and tannic acid induced CaCo-2 cells.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Apoptosis; bcl-2 Homologous Antagonist-Killer Protein; Cell Line, Tumor; Colonic Neoplasms; Fas-Associated Death Domain Protein; Humans; Resveratrol; Stilbenes; Tannins

We have shown that naturally occurring tannins possess antitumor promotion activity in mouse skin. In the present investigation, we studied the ability of a hydrolyzable tannin, gallotannin (GT), and a condensed tannin extracted from red alder (RA) bark to inhibit 1,2-dimethylhydrazine (DMH)-induced colonic aberrant crypt foci (ACF) and tumors in Balb/c mice. In addition, we determined the ability of GT to inhibit the proliferation and to induce apoptosis in a human colon cancer cell line (T-84). Mice were given tannins by intraperitoneal injections, by gavage, or in drinking water before treatment with DMH for 24 weeks. Alternatively, mice were given tannins by intraperitoneal injection or gavage for only 2 weeks before DMH administration, then tannin administration was discontinued and mice were treated with DMH for 24 weeks. The multiplicity, size, and distribution of ACF and tumors were significantly inhibited by GT and RA in the above treatment regimens. The most effective treatments included GT by gavage, RA bark extract by intraperitoneal injection, and either tannin dissolved in drinking water. Extent of inhibition of ACF and tumors was gender independent. In cell culture experiments, GT treatment for three days inhibited the growth of T-84 cells, with a concentration resulting in half-maximal inhibition estimated to be 20 micrograms/ml. The treatment was not cytotoxic to cells at 1-40 micrograms/ml. Interestingly, at 10 micrograms/ml, GT induced apoptosis in T-84 cells as determined by the Hoechst DNA staining technique. Collectively, these findings support a potential role for tannins as chemopreventive agents against colon cancer.

Topics: 1,2-Dimethylhydrazine; Animals; Apoptosis; Carcinogens; Colon; Colonic Neoplasms; Drug Administration Routes; Female; Male; Mice; Mice, Inbred BALB C; Phytotherapy; Precancerous Conditions; Tannins; Tumor Cells, Cultured

Chemopreventive effects of synthetic and naturally occurring antioxidants on heterocyclic amine (HCA)-induced rat carcinogenesis and mechanisms of inhibition were assessed. In a medium-term liver bioassay, combined treatment with 0.03% 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and synthetic antioxidants such as 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), BHA, BHT, tert-butylhydroquinone (TBHQ) and propyl gallate, each at a dose of 0.25%, and troglitazone at doses 0.5 and 0.1%, potently inhibited development of glutathione S-transferase placental form (GST-P) positive foci as compared with MeIQx alone values. Of these antioxidants, HTHQ showed the greatest activity. Green tea catechins tended to inhibit GST-P positive foci development, while quercetin, rutin, curcumin, daidzin, ferulic acid and genistin all exerted significant enhancing effects. HTHQ also inhibited 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colon carcinogenesis in a two stage colon carcinogenesis model using 1,2-dimethylhydrazine (DMH) as an initiator. Immunohistochemically detected PhIP-DNA adduct positive nuclei in the colon induced by continuous oral treatment with 0.02% PhIP for 2 weeks decreased by the combined treatment with 0.5 or 0.125% HTHQ. Methoxyresorfin O-demethylase activity in rat liver microsomes in vitro was clearly inhibited by the addition of HTHQ, BHA, BHT, TBHQ or propyl gallate, with particularly strong inhibition being observed in HTHQ. However, the CYP1A2 level in rat liver increased after oral treatment with HTHQ for 2 weeks. These results indicate that synthetic antioxidants, HTHQ in particular, is a very strong chemopreventor of HCA-induced carcinogenesis. It is suggested that depression of metabolic activation rather than antioxidant activity is responsible for the observed effect. However, other mechanisms, including the effects on phase II enzymes cannot be ruled out.

Topics: Animals; Antioxidants; Carcinogens; Catechin; Colonic Neoplasms; Drug Antagonism; Imidazoles; Liver Neoplasms; Male; Quinolines; Rats; Rats, Inbred F344; Tannins

Protective effects of diets containing cruciferous seed meals or hulls against chemically-induced colon tumors were examined in male CF1 mice. When commercial crambe meal, autolyzed crambe meal, crambe hulls, high glucosinolate rapeseed meal, or canola meal were fed as 12% of the diets of mice injected with 1,2-dimethylhydrazine, 25-80% of the animals developed colon tumors. Animals fed a soybean meal control diet had a 100% tumor rate. Data suggest that cruciferous seed meals may contain a number of compounds that can exert protective effects against tumor formation and growth.

Topics: Animals; Brassicaceae; Colonic Neoplasms; Diet; Dietary Fiber; Glucosinolates; Male; Mice; Phenol; Phytic Acid; Tannins

Topics: Abscess; Barium Sulfate; Carbon Dioxide; Cecal Diseases; Cecal Neoplasms; Colon; Colon, Sigmoid; Colonic Diseases; Colonic Neoplasms; Enema; Hernia, Inguinal; Humans; Intestinal Mucosa; Methods; Polyps; Radiography; Rectum; Tannins; Technology, Radiologic; Water

Topics: Adenocarcinoma; Breast Neoplasms; Colonic Neoplasms; Humans; Intestinal Neoplasms; Kidney Neoplasms; Lung Neoplasms; Microscopy, Electron; Molybdenum; Phosphorus; Rectal Neoplasms; Staining and Labeling; Tannins; Thyroid Neoplasms

Topics: Barium Sulfate; Colonic Neoplasms; Contrast Media; Enema; Humans; Methods; Radiography; Rectal Neoplasms; Tannins; Technology, Radiologic