Anthocyanins and anti-cancer properties -
Rasika Hudlikar, Renyi Wu, David Cheng, Dina Hsiao-Chen Kuo, Lujing Wang, Rebecca Peter, Ran Yin, Shanyi Li, Ah Ng Kong. Ernest Mario School of Pharmacy, Pharmaceutics. Overview Fingerprint. Abstract Anthocyanins are a class of water-soluble flavonoids, which give the intense color to many fruits and vegetables, such as blueberries and red cabbages.
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Together they form a unique fingerprint. View full fingerprint. Cite this APA Author BIBTEX Harvard Standard RIS Vancouver Hudlikar, R. In Natural Products for Cancer Chemoprevention: Single Compounds and Combinations pp. Springer International Publishing. Jump to main content.
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Open access peer-reviewed chapter. Submitted: 27 December Reviewed: 18 Anti-ancer Published: Amti-cancer November com Anthocyanins and anti-cancer properties cbspd. Anthocyanins are one of the Anti-inflammatory diet widespread natural pigments in Anthocyznins plant kingdom. Being surrounded by so many fruits and vegetables rich in anthocyanins, it is recommended to consume a relatively large amount of them. A daily intake of anthocyanins has a certain demonstrated benefits: lowers the risk of cardiovascular disease, diabetes, arthritis, and cancer due, at least in part, to their antioxidant and anti-inflammatory activities.Anthocyanins and anti-cancer properties -
Life Sci. Markakis, P. Anthocyanins as food colors New York: Academic Press , — Mattson, M. Mauray, A. Atheroprotective Effects of Bilberry Extracts in Apo E-Deficient Mice.
Mazewski, C. Comparison of the effect of chemical composition of anthocyanin-rich plant extracts on colon cancer cell proliferation and their potential mechanism of action using in vitro, in silico, and biochemical assays.
Mazza, G. Anthocyanins in Fruits, Vegetables, and Grains: 0 Boca Raton, Ann Arbor, London, Tokyo: CRC press. Mccullough, M. Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults.
Medda, R. Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells. Medzhitov, R. Origin and physiological roles of inflammation. Nature , — Milbury, P. Anthocyanins are bioavailable in humans following an acute dose of cranberry juice.
Min, J. Neuroprotective effect of cyanidinO-glucoside anthocyanin in mice with focal cerebral ischemia. Mink, P. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women.
Mishra, A. Programmed Cell Death, from a Cancer Perspective: An Overview. Diagnosis Ther. Mititelu, R. Inflammatory and Oxidative Stress Markers—Mirror Tools in Rheumatoid Arthritis. Biomedicines 8, Moore, K. Macrophages in the pathogenesis of atherosclerosis.
Cell , — Mpiana, P. In vitro effects of anthocyanin extracts from Justicia secunda Vahl on the solubility of haemoglobin S and membrane stability of sickle erythrocytes.
Blood Transfus 8, — Mulabagal, V. Anthocyanin content, lipid peroxidation and cyclooxygenase enzyme inhibitory activities of sweet and sour cherries. Naseri, R. Anthocyanins in the Management of Metabolic Syndrome: A Pharmacological and Biopharmaceutical Review.
Nussbaum, L. Modern treatment approaches in psychoses. Pharmacogenetic, neuroimagistic and clinical implications. Farmacia 65, 75— Overall, J. Metabolic Effects of Berries with Structurally Diverse Anthocyanins.
Pacheco, S. Padureanu, R. Oxidative stress and inflammation interdependence in multiple sclerosis. Parameshwaran, K. Amyloid beta peptides and glutamatergic synaptic dysregulation. Park, S. Cyanidin and malvidin in aqueous extracts of black carrots fermented with Aspergillus oryzae prevent the impairment of energy, lipid and glucose metabolism in estrogen-deficient rats by AMPK activation.
Genes Nutr. Park, C. Aronia melanocarpa Extract Ameliorates Hepatic Lipid Metabolism through PPARγ2 Downregulation. PloS One Parveen, K.
Evaluation of vegetables and fish oils for the attenuation of diabetes complications. Noisy-le-grand 65, 38— Pascual-Teresa, D. Flavanols and anthocyanins in cardiovascular health: a review of current evidence.
Passamonti, S. The stomach as a site for anthocyanins absorption from food. FEBS Lett. Bioavailability of flavonoids: a review of their membrane transport and the function of bilitranslocase in animal and plant organisms. Drug Metab. Peiffer, D. Chemoprevention of esophageal cancer with black raspberries, their component anthocyanins, and a major anthocyanin metabolite, protocatechuic acid.
Phila 7, — Petroni, K. Dietary cyanidin 3-glucoside from purple corn ameliorates doxorubicin-induced cardiotoxicity in mice. Pham-Huy, L. Free radicals, antioxidants in disease and health. PubMed Abstract Google Scholar.
Pinzaru, I. Stable PEG-coated silver nanoparticles—A comprehensive toxicological profile. Pojer, E. The case for anthocyanin consumption to promote human health: A review. Food Sci. Food Saf. Poulose, S. Anthocyanin-rich acai Euterpe oleracea Mart.
fruit pulp fractions attenuate inflammatory stress signaling in mouse brain BV-2 microglial cells. Pour, P. The signaling pathways, and therapeutic targets of antiviral agents: focusing on the antiviral approaches and clinical perspectives of anthocyanins in the management of viral diseases.
Prior, R. Pratheeshkumar, P. Cyanidinglucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin. Puspita, L. Brain 10, Qin, B. An extract of chokeberry attenuates weight gain and modulates insulin, adipogenic and inflammatory signalling pathways in epididymal adipose tissue of rats fed a fructose-rich diet.
Raj, P. Effects of cyanidin glucoside on cardiac structure and function in an animal model of myocardial infarction. Rehman, S.
Anthocyanins Reversed D-Galactose-Induced Oxidative Stress and Neuroinflammation Mediated Cognitive Impairment in Adult Rats.
Riaz, M. Anthocyanins and human health: biomolecular and therapeutic aspects New York: Springer , — Rice-Evans, C. Antioxidant properties of phenolic compounds. Trends Plant Sci. Roy, M. Action of pelargonidin on hyperglycemia and oxidative damage in diabetic rats: Implication for glycation-induced hemoglobin modification.
Russo, M. Immune Surveillance of the CNS following Infection and Injury. Trends Immunol. Salehi, B. Antioxidants: Positive or Negative Actors?
Biomolecules 8. Cucurbits plants: A key emphasis to its pharmacological potential. Molecules 24, Plant-derived bioactives in oral mucosal lesions: A key emphasis to curcumin, lycopene, chamomile, aloe vera, green tea and coffee properties.
Biomolecules 9, Epibatidine: A Promising Natural Alkaloid in Health. Biomolecules 9, 6. Veronica plants—drifting from farm to traditional healing, food application, and phytopharmacology. The therapeutic potential of Apigenin. Avocado—Soybean Unsaponifiables: A Panoply of Potentialities to Be Exploited.
Biomolecules 10, Salgado, J. The role of black rice Oryza sativa L. in the control of hypercholesterolemia in rats. Food 13, — Santhakumar, A. Consumption of anthocyanin-rich Queen Garnet plum juice reduces platelet activation related thrombogenesis in healthy volunteers.
Foods 12, 11— Sato, D. Black soybean extract reduces fatty acid contents in subcutaneous, but not in visceral adipose triglyceride in high-fat fed rats. Sesso, H. Strawberry intake, lipids, C-reactive protein, and the risk of cardiovascular disease in women.
Seymour, E. Blueberry intake alters skeletal muscle and adipose tissue peroxisome proliferator-activated receptor activity and reduces insulin resistance in obese rats. Food 14, — Shah, S. Protection of the Developing Brain with Anthocyanins Against Ethanol-Induced Oxidative Stress and Neurodegeneration.
Sharifi-Rad, J. In vitro and in vivo assessment of free radical scavenging and antioxidant activities of Veronica persica Poir. Diet, Lifestyle and Cardiovascular Diseases: Linking Pathophysiology to Cardioprotective Effects of Natural Bioactive Compounds.
Public Health 17, Sharifi-Rad, M. Lifestyle, Oxidative Stress and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics. Shih, P. Antioxidant and cognitive promotion effects of anthocyanin-rich mulberry Morus atropurpurea L.
Protective effects of anthocyanins against amyloid beta-peptide-induced damage in neuro-2A cells. Shin, W. Protective effect of anthocyanins in middle cerebral artery occlusion and reperfusion model of cerebral ischemia in rats.
Singh, A. Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Skates, E. Berries containing anthocyanins with enhanced methylation profiles are more effective at ameliorating high fat diet-induced metabolic damage. Sogo, T. Comparison of the Inhibitory Effects of Delphinidin and Its Glycosides on Cell Transformation.
Planta Med. Song, N. Cyanidin suppresses neoplastic cell transformation by directly targeting phosphatidylinositol 3-kinase.
Song, H. Mulberry ethanol extract attenuates hepatic steatosis and insulin resistance in high-fat diet-fed mice. Speciale, A. Nutritional antioxidants and adaptive cell responses: an update.
CyanidinO-glucoside counters the response to TNF-alpha of endothelial cells by activating Nrf2 pathway. Stewart, C. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer.
Strathearn, K. Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinsons disease. Subhramanyam, C. Microglia-mediated neuroinflammation in neurodegenerative diseases. Cell Dev. Sui, X. Impact of Food Processing on Anthocyanins New York: Springer.
Sun, H. Slow and selective death of spinal motor neurons in vivo by intrathecal infusion of kainic acid: implications for AMPA receptor-mediated excitotoxicity in ALS.
Swinburn, B. A Lancet Commission on obesity. Lancet , — Szydlowska, K. Calcium, ischemia and excitotoxicity. Cell Calcium 47, — Takikawa, M.
Dietary Anthocyanin-Rich Bilberry Extract Ameliorates Hyperglycemia and Insulin Sensitivity via Activation of AMP-Activated Protein Kinase in Diabetic Mice. Talavera, S. Anthocyanins are efficiently absorbed from the stomach in anesthetized rats.
Anthocyanins are efficiently absorbed from the small intestine in rats. Tarone, A. Anthocyanins: New techniques and challenges in microencapsulation.
Thompson, K. The effect of anthocyanin supplementation in modulating platelet function in sedentary population: a randomised, double-blind, placebo-controlled, cross-over trial. Anthocyanin supplementation in alleviating thrombogenesis in overweight and obese population: A randomized, double-blind, placebo-controlled study.
Foods 32, — Tomay, F. Purple corn extract induces long-lasting reprogramming and M2 phenotypic switch of adipose tissue macrophages in obese mice.
Toufektsian, M. Chronic dietary intake of plant-derived anthocyanins protects the rat heart against ischemia-reperfusion injury. Dietary flavonoids increase plasma very long-chain n-3 fatty acids in rats. Tsai, T. An Anthocyanin-Rich Extract from Hibiscus sabdariffa Linnaeus Inhibits N -Nitrosomethylurea-Induced Leukemia in Rats.
Tsatsakis, A. A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse. Tsuda, T. Cyanidin 3-O-beta-D-glucoside suppresses nitric oxide production during a zymosan treatment in rats.
Tokyo 48, — Dietary cyanidin 3-O-beta-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. Anthocyanin enhances adipocytokine secretion and adipocyte-specific gene expression in isolated rat adipocytes.
Dietary anthocyanin-rich plants: biochemical basis and recent progress in health benefits studies. Ullah, I. Anthocyanins protect against kainic acid-induced excitotoxicity and apoptosis via ROS-activated AMPK pathway in hippocampal neurons.
CNS Neurosci. Ullah, R. Natural Antioxidant Anthocyanins-A Hidden Therapeutic Candidate in Metabolic Disorders with Major Focus in Neurodegeneration. Nutrients Vaidyanathan, J.
Transport and metabolism of the tea flavonoid - -epicatechin by the human intestinal cell line Caco Van Langenhove, T. The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum. Vendrame, S. Wild blueberry Vaccinium angustifolium consumption improves inflammatory status in the obese Zucker rat model of the metabolic syndrome.
Virgili, F. Regulation of cellular signals from nutritional molecules: a specific role for phytochemicals, beyond antioxidant activity. Free Radic.
Vivarelli, F. The combined effect of Sango sprout juice and caloric restriction on metabolic disorders and gut microbiota composition in an obesity model. Wallace, T. Anthocyanins in health and disease Boca Raton: CRC Press. Walton, M. The flavonol quercetinglucoside inhibits cyanidinglucoside absorption in vitro.
The Flavonol QuercetinGlucoside Inhibits CyanidinGlucoside Absorption in Vitro. Wang, D. Protocatechuic acid, a metabolite of anthocyanins, inhibits monocyte adhesion and reduces atherosclerosis in apolipoprotein E-deficient mice. Wang, X. Acta , — Warner, L. Handbook of Anthocyanins: Food Sources, Chemical Applications and Health Benefits Incorporated: Nova Science Publishers.
Wei, H. Cardioprotective Effects of Malvidin Against Isoproterenol-Induced Myocardial Infarction in Rats: A Mechanistic Study. Monitor 23, — Wei, J. Anthocyanins from Black Chokeberry Aroniamelanocarpa Elliot Delayed Aging-Related Degenerative Changes of Brain.
Winter, A. An anthocyanin-enriched extract from strawberries delays disease onset and extends survival in the hSOD1 G93A mouse model of amyotrophic lateral sclerosis. Wu, X. Dietary Blueberries Attenuate Atherosclerosis in Apolipoprotein E-Deficient Mice by Upregulating Antioxidant Enzyme Expression.
Wu, T. Anti-obesity effects of artificial planting blueberry Vaccinium ashei anthocyanin in high-fat diet-treated mice. Mulberry and cherry anthocyanin consumption prevents oxidative stress and inflammation in diet-induced obese mice. Wyspianska, D. Effect of microencapsulation on concentration of isoflavones during simulated in vitro digestion of isotonic drink.
Xia, M. Supplementation of diets with the black rice pigment fraction attenuates atherosclerotic plaque formation in apolipoprotein E deficient mice. Xia, X. An anthocyanin-rich extract from black rice enhances atherosclerotic plaque stabilization in apolipoprotein E-deficient mice.
Xia, Y. NF- B, an Active Player in Human Cancers. Cancer Immunol. Xie, L. Recent advances in understanding the anti-obesity activity of anthocyanins and their biosynthesis in microorganisms.
Trends Food Sci. Yang, Y. Anthocyanin extract from black rice significantly ameliorates platelet hyperactivity and hypertriglyceridemia in dyslipidemic rats induced by high fat diets.
Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis. Ye, J. Effect of purple sweet potato anthocyanins on beta-amyloid-mediated PC cells death by inhibition of oxidative stress.
Yin, M. Aqueous Extract of Gynura Bicolor Attenuated Hepatic Steatosis, Glycative, Oxidative, and Inflammatory Injury Induced by Chronic Ethanol Consumption in Mice.
Youdim, K. Incorporation of the elderberry anthocyanins by endothelial cells increases protection against oxidative stress.
Free Radical Biol. Potential role of dietary flavonoids in reducing microvascular endothelium vulnerability to oxidative and inflammatory insults.
Zhang, W. FASEB J. Zhang, B. Anthocyanins from Chinese bayberry extract protect beta cells from oxidative stress-mediated injury via HO-1 upregulation. Zhang, Z. Purple sweet potato color attenuates hepatic insulin resistance via blocking oxidative stress and endoplasmic reticulum stress in high-fat-diet-treated mice.
Zhang, X. Effects of purified anthocyanin supplementation on platelet chemokines in hypocholesterolemic individuals: a randomized controlled trial. Lond 13, Zhang, J. Neuroprotective effects of anthocyanins and its major component cyanidinO-glucoside C3G in the central nervous system: An outlined review.
Zhao, M. Blueberry anthocyanins extract inhibits acrylamide-induced diverse toxicity in mice by preventing oxidative stress and cytochrome P 2E1 activation. Foods 14, 95— Zhou, J.
Black rice-derived anthocyanins inhibit HERpositive breast cancer epithelial-mesenchymal transition-mediated metastasis in vitro by suppressing FAK signaling. Zhou, L. Zhu, W. The anthocyanin cyanidinO-β-glucoside, a flavonoid, increases hepatic glutathione synthesis and protects hepatocytes against reactive oxygen species during hyperglycemia: Involvement of a cAMP-PKA-dependent signaling pathway.
Ziberna, L. Acute cardioprotective and cardiotoxic effects of bilberry anthocyanins in ischemia-reperfusion injury: beyond concentration-dependent antioxidant activity.
Transport and bioactivity of cyanidin 3-glucoside into the vascular endothelium. Keywords: anthocyanins, biodisponibility, neuroprotective, cardioprotective, antiobesity, antidiabetic, antioxidant, anticancer.
Citation: Salehi B, Sharifi-Rad J, Cappellini F, Reiner Ž, Zorzan D, Imran M, Sener B, Kilic M, El-Shazly M, Fahmy NM, Al-Sayed E, Martorell M, Tonelli C, Petroni K, Docea AO, Calina D and Maroyi A The Therapeutic Potential of Anthocyanins: Current Approaches Based on Their Molecular Mechanism of Action.
Received: 29 May ; Accepted: 05 August ; Published: 26 August Copyright © Salehi, Sharifi-Rad, Cappellini, Reiner, Zorzan, Imran, Sener, Kilic, El-Shazly, Fahmy, Al-Sayed, Martorell, Tonelli, Petroni, Docea, Calina and Maroyi. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY.
The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.
No use, distribution or reproduction is permitted which does not comply with these terms. sharifirad gmail. com ; Miquel Martorell, mmartorell udec. cl ; Katia Petroni, katia. petroni unimi. it ; Daniela Calina, calinadaniela gmail.
com ; Alfred Maroyi, amaroyi ufh. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
Detailed analysis of intestinal microbiota composition 16S ribosomal RNA sequencing of caecum content revealed the reduced expression of pro-inflammatory Bilophila wadsworthia in AC-functional sausage group if compared to control sausage group Fernández et al.
The palm tree fruit açaì, growing in South America, has a high content of AC 3. AP also decreased cell proliferation in tumors Ki staining and increased expression of tumor suppressor genes, such as Dlc1, Akt3, and the anti-inflammatory genes Ppara Fragoso et al.
The adenomatous polyposis coli APC min mice model, a standard experimental CRC model for preclinical trials, presents a mutation in the murine homolog of the human APC tumor suppressor gene.
As a result, mice develop multiple neoplasms predominantly in the small intestine. Sweet potato extracts were significantly more efficient in diminishing polyp numbers than the flesh-or skin-supplemented diet. The number of polyps in colon was even increased with skin and ARE-supplemented diets, showing their inability to counteract carcinogenesis Asadi et al.
Non-steroidal anti-inflammatory drugs demonstrated to be effective in cancer prevention. Nevertheless, their prolonged use can cause intestinal tract damage. It has been suggested that their combined use with phytochemicals may improve CRC prevention.
APC min mice fed with either lyophilized tart cherry ACs including cyanidin 3-O-sambubioside and other complex glycosides of cyanidin or pure cyanidin had different responses on tumor frequency and volume, depending on the intestinal tract area.
In the caecal part, adenomas were significantly fewer and smaller in animals fed with either extracts or the pure aglycone with respect to mice consuming the control diet or sulindac, a non-steoidal anti-inflammatory drug.
The same treatment had no significant effect on colonic tumor volume or number Kang et al. A combined diet of AC-rich tart cherry extract with sulindac given to APC min mice resulted in lower tumor number and smaller total tumor area per mouse in small intestine with respect to mice fed sulindac alone.
These observations were AC dose-independent. Adenomas were mostly distributed in the medial and distal sections of the small intestine, with very few lesions in colon Cooke et al.
Contrarily to preclinical studies, human studies did not demonstrate encouraging data on the relation between AC-rich diets and prevention of CRC. In the interventional study performed by Thomasset et al. The authors had performed preliminary pharmacokinetic studies and identified AC, their methyl and glucuronide metabolites in plasma, colorectal tissue, and urine, but not in the liver.
In the pharmacodynamic part of the investigation, they found that the concentration of circulating procarcinogenic Insulin-like growth factor 1 IGF-1 was not significantly reduced.
Mirtocyan did not affect the levels of oxidative DNA damage biomarkers. A prospective cohort study on middle-aged Finnish men, with mean flavonoid intake of A retrospective case-control study was performed by including both CRC patients and healthy controls.
Eating habits were recorded through. Dietary intake data were collected every 4 years through food-frequency questionnaire Nimptsch et al. We have retrieved 10 articles reporting molecular mechanisms of AC-related anticancer activity. Table 7 summarizes features that give information related to this topic.
Early-stage colon cancer cells HCT were used in five studies, whereas four studies used cells associated with advanced stage colon cancer, such as HT Two studies reported data obtained from Caco-2 cells, regarded as a model of differentiated intestinal epithelium; one study used non-cancer colon fibroblast cells, i.
Table 7 Features of included articles reporting AC-related anticancer molecular mechanism. Concentrations of AC ranged from 0.
Studies showed mostly positive actions of AC on processes involved in carcinogenesis, like apoptosis, inflammation, proliferation, tight junction modulation, oxidative stress, and tumor number.
Phenolic-rich extracts, rather than AC alone, were able to inhibit proliferation of human colon cancer cell lines, such as HT and HCT, pointing to the existence of potential synergic actions of different polyphenols Mazewski et al.
On the other hand, the same authors concluded that two pure AC molecules, i. By targeting this receptor, both molecules showed to interfere with the delicate balance of two opposed processes, like cancer cell survival and programmed cell death.
Cyanidin 3-glucoside was also more efficient in reducing adenoma numbers in small intestine than the AC-rich bilberry extract Cooke et al. Cancer cells have both a huge proliferative potential and impaired mechanisms of apoptosis.
Some authors Yun et al. They examined the mechanism s by which the delphinidin aglycone is able to induce apoptosis in HCT cell line. Delphinidin treatment induced activation of caspases and PARP cleavage, two authentic mechanisms of apoptotic response.
Delphinidin treatment resulted in a significant increase in proapoptotic protein Bax and decrease in antiapoptotic protein Bcl-2, leading to cell cycle arrest. Delphinidin also upregulated the expression of both the tumor suppressor protein p53 and its downstream target p It caused downregulation of both cyclin B1 and cdc2, again leading to cell cycle arrest.
They found that delphinidin treatment of HCT caused downregulation of the NF-κB pathway, as shown by decreased expression of the p65 subunits of NF-κB, reduced IκB phosphorylation, and inhibited nuclear translocation of NF-κB.
In studies on the human colon cancer HT cell line, some authors Jang et al. Cells exposed to 50 µM H 2 O 2 for 24 h showed significant expression of PGK1. Interestingly, cells co-treated with delphinidin had attenuated expression of this protein. High levels of PGK1 are associated with tumor survival and angiogenesis.
These authors suggested that the antioxidant potential of delphinidin could contribute to anti-cancer strategy.
The apoptotic signaling pathway was also explored in HCT cells Shin et al. The authors observed decreased expression of pro-caspase-3, -8, and -9, activation of caspase-3 and PARP cleavage.
AIMs reduced the expressions of anti-apoptotic proteins XIAP, cIAP-1, and cIAP-2 , so promoting cell death. Other apoptotic pathways were influenced by AIMs through increased pMAPK phosphorylation and attenuated JNK phosphorylation.
Some authors suggested that the chemical structure of AC could strongly influence their biological function Renis et al. They used human colon carcinoma CaCo-2 cells and two ACs, i. Reactive oxygen species ROS were found to be elevated in almost all cancers.
Cancer cells balance ROS levels with anti-oxidative enzymes levels in favor of their own proliferation and survival. CY3G was more efficient than CY in counteracting the H 2 O 2 -induced DNA damage.
Specific mutagenic lesions occurring after exposure to ROS were removed by 8-oxoguanine DNA glycosylase OGG1 a DNA repair enzyme. Heat shock proteins HSP70 are highly expressed in CaCo-2 cells and their expression was even more increased when the cells were treated with CY3G or CY.
The same pattern of increased expression of cell cycle-related proteins, such as Ataxia telangiectasia mutated gene ATM , p53, and topoisomerase IIβ, was obtained by both CY3G and CY. The authors have proposed an explanation, i.
Metabolic alterations in cancer cells can lead to high metabolic activity and increased proton production. Briviba et al. Proton extrusion is proposed to be involved in cell growth Di Sario et al.
This process was inhibited by cyanidin 10 µM , but by none of its glycosides, i. Cyanidin did not change extracellular-signal-regulated kinase ERK phosphorylation.
Cocoplum anthocyanins CP have been demonstrated to exercise anti-inflammatory activity in both human cancer cells HT and inflamed benign cells Venancio et al. Inflammation is closely related with carcinogenesis.
Persistent inflammation favors growth and inhibition of apoptosis in transformed cells. CCDCo colon fibroblasts were selected for their low levels of ROS. Thus, experimental induction of inflammation could be monitored by measurable intracellular increases of ROS.
TNF-α-induced inflammation measured as ROS production in these non-malignant colon fibroblasts was significantly decreased with CP extract. After this treatment, NF-κB1 mRNA expression was decreased with CP extract, along with protein expression of TNF-α, IL1β, and IL The authors also reported decreased mRNA expression of inflammatory mediators NF-κB1, TNF-α, IL1β, and IL-6 in HT colon cancer cells after CP treatment, whereas protein expression decrease was observed only for TNF-α.
In the studies conducted in HCT Shin et al. Preservation of TJ integrity and inhibition of proteolytic digestion of the extra cellular matrix is important to prevent tumor cell mobility and invasiveness.
In functional assays, anthocyanins AC also exerted potential anticancer activity. The AC mix increased TJs tightening, measured as transepithelial electrical resistance. The same AIM concentration was successful in diminishing the HCT cells capability to penetrate ECM.
Concerning the general question whether AC prevent or not CRC in vivo , the detailed analysis of the literature enabled to provide some answer to the initially defined questions, as follows:.
We were able to identify four studies involving human subjects: one interventional study Thomasset et al. A synopsis of these studies is presented in Table 8. The reported effects of AC were, however, controversial.
No dose dependence could be found, since, two higher doses gave no significant decrease. Other carcinogenesis-related markers, such as serum IGF-I levels, oxidative DNA damage or apoptotic index, were not affected. The authors recognized that they tried elevated doses of AC, 0.
While one of these studies Xu et al. Two prospective cohort studies found no AC effect. Taken together, these studies showed weak or no correlation between AC intake and CRC risk decrease.
As many as 15 intervention studies tested the role of AC in CRC prevention in different murine strains, i. Animals were fed with standard rodent food in combination with supplements enriched with AC extracts or fruits.
The AC supplementation ranged from µg to g. In some studies, though, the doses of AC consumed by animals could not be calculated. A synopsis of these studies is in Table 9. With the exception of the mouse Apc Min model a knockout for the human homologue of the tumor suppressor APC gene , all murine strains were investigated after chemical induction of CRC lesions of different tumor stages.
In seven studies, AC treatments were more efficient on ACF rather than on developed cancers. Here, four studies showed that the preventive effect of AC was predominantly on adenomas rather than on adenocarcinomas, suggesting that AC may be most effective at early tumor stages.
These animal models have both advantages for short-term pre-clinical screening goals and disadvantages related to differences in lifespan, the diet and environmental exposure of human and murine species.
Thus, experimental design in murine models of induced CRC and interpretation of results must take these differences in due consideration Femia and Caderni, Concerning the molecular mechanisms whereby AC prevent CRC in vivo , the analysis of the included articles enabled to give answers to our research interests, as follows:.
Only nine articles complying with the inclusion criteria reported in vitro studies on the molecular mechanisms by which AC inhibit CRC progression, as outlined in Table HCT cells, as a model of early stage colon cancer, were used for studies of proliferation, apoptosis and tight junction modifications.
HT cells, as a model of colorectal adenocarcinoma, were used in studies of metabolic activation, inflammatory processes, and intracellular oxidative status. These cells were used to test AC cytotoxicity and inhibition of basal cellular ROS production. As shown in Table 10 , six pure molecules were tested, i.
AC were shown to alter several fundamental processes that play a key role in cell cycle control and carcinogenesis, as listed in Table 11 and illustrated in Figure 2.
Only two studies assessed the direct interaction of AC molecules with molecular targets, such as EGFR Mazewski et al. By contrast, all the other studies focused on downstream effects, mostly assessed as changes in the levels of signaling components regarded as markers of AC-dependent effects.
By this approach, it is however impossible to infer the primary cause of molecular marker changes, because of cross talk involving several signaling pathways. Only one marker was described as being in straight correlation with delphinidin treatment of cancer cells, i.
Table 8 Human populations or groups surveyed for assessing the relationship linking AC intake to CRC. Table 9 List of animal models used in intervention studies for assessing the relationship linking AC intake to CRC. Table 10 List of experimental models used to identify the molecular mechanisms of CRC prevention by AC not diets or not supplements.
Table 11 List of biological processes reactions, pathways, or functions modified by AC. With this systematic review we aimed at bringing to light the actual state of the art in the research exploring AC-specific CRC prevention and the underlying oncotargets.
AC have shown to protect against early-stage cancer lesions in experimental animals, but not in humans. Several studies in CRC cell models have shown AC to affect cellular processes related to cell cycle and transformation. However, these effects cannot yet be ascribed to AC-specific molecular interactions with CRC oncotargets, but rather to complex effects resulting in preventing intestinal cells from entering in the cell fate of neoplastic transformation.
We believe that this overview may serve the scientific community to properly select the experimental models and conditions to further clarify the mode of action of AC and their degradation products in modulating the carcinogenetic process in CRC.
Publicly available datasets were analyzed in this study. SP designed the method, created and managed the database of the PubMed search output. NM carried out all phases of the systematic review. Both NM and FT independently screened and assessed the included articles.
NM and SP drafted the article. The data was graphed in the form of percentage inhibition vs. concentration of each component. Proof of the quantitative ability of the viability stain is shown in Figs. To calculate percentage inhibition, first the cell counts were multiplied by to account for the dilution of adding the PI stain, as well as the volume of the analyzed sample being 10 µl.
The mean of multiple replicates 4 — 6 ± the standard deviation were then determined. All well volumes were µl, where µl of the tumor cells had 50 µl of the supplements at different concentrations added to their respective wells in well plates Falcon Plastics, Brookings, SD, USA.
A 48 h incubation started with 5×10 4 cells and ended with about 6—7×10 4 cells. The initial 48 h incubation allowed the cells to enter exponential growth. The test supplements at various concentrations were added in 50 µl to the appropriate wells.
In the process of developing the viability assay used in this paper, K cells were heated at 56°C in µl aliquots at 5 min intervals up to 20 min. Each sample had µl of the PI-viability stain added and analyzed by flow cytometry within 30 min at room temperature 22—24°C.
In Fig. Furthermore as shown in Fig. The control, viable PI population curve came to a baseline on the left of the curve, which was the beginning of the viable cell population fluorescent staining. The dead cells were to the right of the vertical line. At Day 10, dead cells were detected in the positive PI fluorescence portion of the histogram.
By Days 14—18, two distinct populations of dead cells were seen, which showed the cells where the cell membrane was compromised peak to the left of the vertical line and cells where the nuclear membrane was compromised peak to the right of the vertical line.
This showed the PI had intercalated into the double-stranded nucleic acids, causing a very large increase in fluorescent yield. At Day 18, all of the cells were dead. There is over a 1,fold increase in fluorescence, which is indicative of the high fluorescence yield due to the intercalation of the Pl into the double stained nucleic acids.
The Bilberry NNS Measurements showed a greatly enhanced potent activity when these compounds were encapsulated in the liposomal structure. These samples were run on the Malvern Zetasizer ZSP with a backscattering angle of degrees to measure the particle size by dynamic light scattering.
A non-negative least squares algorithm was used to generate the size distribution by intensity. Samples were run as six replicates. Standard deviation and mean diameters are shown. The maximum percentage inhibition results occurred after an exposure for A 2 days 48 h as compared to B 3 days 72 h from 0—4.
By Day 3, the percentage inhibition curve between 0 and 4. A dramatic increase in the inhibition of the cancer cells was seen between Day 2 and 3.
The LD 50 in two experiments were 0. The published data shows the LD 50 is ~0. This shows an increase in the cytotoxicity of the Bilberry NNS of 8—40 times the published free bilberry.
Detailed range from 0. Two LD50 of 0. The most promising anticarcinogenic agents in plants are phenolic compounds, which are abundantly present in Bilberries Vaccinium myrtillus , and a variety of others including lingonberry Vacciniumvitis-idaea , and cloudberry Rubus chamaemorus 3 , 6 — 8.
Anthocyanins are hydrophilic compounds, predictably unable to cross the cell plasma membrane by passive diffusion 9. The results obtained show that the bilberry extract does have an increased anti-cancer effect when it is encapsulated compared to the free compound.
Experiments were performed to determine if there was an effect, first of all, and then when that effect was strongest. As shown in Fig. However, at 96 h, the results were similar to the 24 h percentage inhibition curve due to, in part, the metabolic destruction of the anthocyanins and cell culture nutritional depletion.
Besides its role in fighting cancer, Bilberry is an effective support against type 2 Diabetes 12 — 15 , vision improvement 16 — 18 , obesity 19 — 21 , cancer prevention 22 — 24 , ulcerative colitis 25 , anti-inflammatory 26 , 27 , antioxidant 28 , 29 , and gingival inflammation In conclusion, the direct cytotoxic effects of the NNS Bilberry showed LD 50 levels 8—40 times lower than what is required for the Bilberry that is not encapsulated.
The increase in bioavailability with the Bilberry NNS and its water solubility show the feasibility of using Bilberry NNS in cancer patient clinical trials. Furthermore, the NNS Bilberry can be used as a preventive supplement that is freely water soluble, consisting of a micelle formulation that is 5.
The stability of this NNS preparation enables its combination with other NNS supplements by simply adding drops together in a beverage. Some of the NNS preparations that have been successfully micellized using the NNS methodology include Vitamins C, B12, D 3 , E , CQ 10 , Curcumin, Artemisinin, Frankincense, Riboside Nucleotide, Acemanan, among others.
The present study was conducted at the Cancer Research Institute of West Tennessee, under the direction of Dr Jerry Thornthwaite, who provided all of the materials and equipment used. This research was supported in part by generous donations from Mr. Henry Respess, The Shumard Foundation and the Carter Family Trust.
We thank Dr Carrie Schindler for the Malvern Zetasizer Nano System analyses of the sizing of the NutraNanoSpheres. We thank Dr Tony Kirk, and Bonita Thornthwaite for reviewing this manuscript.
Thomasset S, Berry DP, Cai H, West K, Marczylo TH, Marsden D, Brown K, Dennison A, Garcea G, Miller A, et al: Pilot study of oral anthocyanins for colorectal cancer chemoprevention.
Cancer Prev Res Phila. Sehitoglu MH, Farooqi AA, Qureshi MZ, Butt G and Aras A: Anthocyanins: Targeting of signaling networks in cancer cells. Asian Pac J Cancer Prev. Sci Rep. Kausar H, Jeyabalan J, Aqil F, Chabba D, Sidana J, Singh IP and Gupta RC: Berry anthocyanidins synergistically suppress growth and invasive potential of human non-small-cell lung cancer cells.
Cancer Lett. Nguyen V, Tang J, Oroudjev E, Lee CJ, Marasigan C, Wilson L and Ayoub G: Cytotoxic effects of bilberry extract on MCF7-GFP-tubulin breast cancer cells. J Med Food. J Nutr.
Asia Pac J Clin Nutr. Wang Y, Zhao L, Lu F, Yang X, Deng Q, Ji B and Huang F: Retinoprotective effects of bilberry anthocyanins via antioxidant, anti-inflammatory and anti-apoptotic mechanisms in a visible light-induced retinal degeneration model in pigmented rabbits.
a School of Anthocyanins and anti-cancer properties Science and Engineering, Wuhan Anthocyankns University, Wuhan, China. fernandes fc. Planned eating intervals Hubei Collaborative Anti-cancdr Center for Processing Antocyanins Anthocyanins and anti-cancer properties Products, Anhhocyanins, China E-mail: jingren. he whpu. In this study, the gastric transport efficiency of malvidinglucoside and several derivatives was assayed on the MKN cell model. The transport efficiency was found to increase for all compounds with the incubation time. Pyranoanthocyanins may slightly impair transport efficiency levels in comparison with native anthocyanins. Cancer stands among the main antic-ancer of anti-camcer worldwide characterized by a combination of Improving skin elasticity factors anti-canxer drive tumor progression and invasiveness. Oxidative Anthocyanins and anti-cancer properties has been shown Anthocyanins and anti-cancer properties Anthocyamins a central involvement in cancer porperties for promoting an Enhance metabolism naturally microenvironment, favoring DNA mutations and damage to biological structures. Flavonoids are naturally occurring compounds present in plant-based foods, mainly fruits and vegetables, which exhibit notable antioxidant and radical scavenging activities. Due to their biological activities and their availability in nature, anthocyanins and flavonols, one of the flavonoids subclasses, have been studied as potential anticarcinogenic agents. This chapter summarizes the main therapeutic implications of some of the most efficacious diet-derivate anthocyanidins and flavonols, and its glycosides, on cancer chemotherapy and chemoprevention.
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