cryptoxanthins and Disease-Models--Animal

To better understand the potential function of carotenoids in the chemoprevention of cancers, mechanistic understanding of carotenoid action on genetic and epigenetic signaling pathways is critically needed for human studies. The use of appropriate animal models is the most justifiable approach to resolve mechanistic issues regarding protective effects of carotenoids at specific organs and tissue sites. While the initial impetus for studying the benefits of carotenoids in cancer prevention was their antioxidant capacity and pro-vitamin A activity, significant advances have been made in the understanding of the action of carotenoids with regards to other mechanisms. This review will focus on two common carotenoids, provitamin A carotenoid β-cryptoxanthin and non-provitamin A carotenoid lycopene, as promising chemopreventive agents or chemotherapeutic compounds against cancer development and progression. We reviewed animal studies demonstrating that β-cryptoxanthin and lycopene effectively prevent the development or progression of various cancers and the potential mechanisms involved. We highlight recent research that the biological functions of β-cryptoxanthin and lycopene are mediated, partially via their oxidative metabolites, through their effects on key molecular targeting events, such as NF-κB signaling pathway, RAR/PPARs signaling, SIRT1 signaling pathway, and p53 tumor suppressor pathways. The molecular targets by β-cryptoxanthin and lycopene, offer new opportunities to further our understanding of common and distinct mechanisms that involve carotenoids in cancer prevention. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.

Topics: Animals; Antioxidants; Beta-Cryptoxanthin; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Humans; Lycopene; Neoplasms; NF-kappa B; Sirtuin 1; Tumor Suppressor Protein p53

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is considered a hepatic manifestation of metabolic syndrome; however, mechanisms underlying the onset and progression of NAFLD are still unclear. Resident and recruited macrophages are key players in the homeostatic function of the liver and in the progression of NAFLD to NASH. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of macrophages. New NAFLD therapies will likely involve modification of macrophage polarization by restraining M1 activation or driving M2 activation. Carotenoids are potent antioxidants and anti-inflammatory micronutrients that have been used to prevent and treat NAFLD. In addition to their antioxidative action, carotenoids can regulate macrophage polarization and thereby halt the progression of NASH. In this review, we summarize the molecular mechanisms of macrophage polarization and the function of liver macrophages/Kupffer cells in NAFLD. From our review, we propose that dietary carotenoids, such as β-cryptoxanthin and astaxanthin, be used to prevent or treat NAFLD through the regulation of macrophage polarization and liver homeostasis.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Beta-Cryptoxanthin; Carotenoids; Cell Polarity; Disease Models, Animal; Disease Progression; Homeostasis; Humans; Kupffer Cells; Liver; Macrophage Activation; Metabolic Syndrome; Micronutrients; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic; Xanthophylls

β-Cryptoxanthin and astaxanthin are antioxidant carotenoid pigments that inhibit lipid peroxidation as potently as vitamin E. We hypothesized that acute treatment with β-cryptoxanthin and astaxanthin causes similar reductions in the sizes of cardiac infarcts caused by ischemia-reperfusion (I/R) injury by attenuating oxidative stress and cardiac mitochondrial dysfunction.. C57BL/6 mice (n = 36) were randomized to receive vehicle, β-cryptoxanthin, astaxanthin, or vitamin E at 50 mg/kg by gavage feeding prior to I/R injury. Cardiac I/R was induced by left anterior descending coronary artery ligation followed by reperfusion. All treatments significantly reduced infarct sizes by 36-57%, attenuated apoptosis and also attenuated cardiac mitochondrial dysfunction in the treated groups compared to the control group. Although astaxanthin and vitamin E exhibited similar efficacy with respect to cardioprotection, β-cryptoxanthin exhibited greater efficacy than its counterparts, as it reduced infarct sizes by 60%. β-Cryptoxanthin was more effective than astaxanthin and vitamin E because it reduced cardiac mitochondrial swelling, mitochondrial depolarization, the Bax/Bcl-2 ratio, and plasma and cardiac thiobarbituric acid reactive substances levels more significantly than its counterparts.. Acute β-cryptoxanthin treatment exhibits greater cardioprotective efficacy against I/R injury than astaxanthin and vitamin E by reducing infarct sizes and attenuating apoptosis, oxidative stress, and mitochondrial dysfunction.

Topics: Animals; Beta-Cryptoxanthin; Cardiotonic Agents; Disease Models, Animal; Heart; Male; Membrane Potential, Mitochondrial; Mice; Mice, Inbred C57BL; Mitochondrial Diseases; Myocardial Infarction; Myocardial Reperfusion Injury; Oxidative Stress; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances; Vitamin E; Xanthophylls

β-cryptoxanthin is a common carotenoid pigment found in fruit, especially in Satsuma mandarins and in persimmons. After ingestion, β-cryptoxanthin is distributed to and accumulates in organs, such as the liver, lung, and kidney. Recent studies have reported that because of its antioxidant defense, β-cryptoxanthin performs several important functions in the preservation of human health and in the prevention of several diseases, including cancer and osteoporosis. The present study aims to determine whether β-cryptoxanthin has a protective effect on renal glomeruli during acute nephritis. To develop our acute nephritis mouse model, we induced kidney inflammation in mice using lipopolysaccharide. To analyze pathological changes in the renal glomeruli of these mice, tissue sections of the kidney were analyzed by hematoxylin-eosin and periodic acid-Schiff staining. In mice with acute nephritis, we observed a thickening of the basal membrane in the renal glomeruli. By ultrastructural analysis, abnormalities in the foot cells were also identified. In the β-cryptoxanthin-ingested mice, these pathological changes were decreased. Migration of urinal proteins occurred in mice with acute nephritis, but this was decreased in β-cryptoxanthin-ingested mice, such that it correlated with the blood concentration of β-cryptoxanthin. Furthermore, in β-cryptoxanthin-ingested mice, both the accumulation and activation of inflammatory cells were decreased in the renal glomeruli. These results suggest that β-cryptoxanthin ingestion may produce great improvement in acute nephritis. These findings provide new insights into β-cryptoxanthin and its protective effect, and provide a new target for pharmacological therapy in human disease.

Topics: Acute Disease; Administration, Oral; Animals; Antioxidants; Beta-Cryptoxanthin; Citrus sinensis; Disease Models, Animal; Kidney Glomerulus; Lipopolysaccharides; Male; Mice, Inbred C57BL; Nephritis; Tissue Distribution

The acquired resistance to chemotherapy represents the major limitation in the treatment of cancer. New strategies to solve this failure and improve patients' outcomes are necessary. The cancer preventive effect of β-cryptoxanthin has been widely described in population studies. Few reports support its putative use as an antitumoral compound. Here we focus on the therapeutic potential of β-cryptoxanthin individually or in combination with oxaliplatin in colon cancer and try to decipher the molecular basis underlying its effect.. Apoptosis, viability and proliferation assays, mouse models, and an intervention study in 20 healthy subjects were performed. A PCR array was carried out to unravel the molecular putative basis of the β-cryptoxanthin effect, and further signaling experiments were conducted. Comet Assay was completed to evaluate the genotoxicity of the treatments.. β-Cryptoxanthin differentially regulates the expression of the P73 variants in vitro, in vivo, and in a human intervention study. This carotenoid decreases the proliferation of cancer cells and cooperates with oxaliplatin to induce apoptosis through the negative regulation of ΔNP73. The antitumoral concentrations of oxaliplatin decrease in the presence of β-cryptoxanthin to achieve same percentage of growth inhibition. The genotoxicity in peripheral blood mononuclear cells of mice decreased in the combined treatment.. We propose a putative novel therapeutic strategy for the treatment of colon cancer based on the combination of β-cryptoxanthin and oxaliplatin. The combined regimen produced more benefit than either individual modality without increasing side effects. In addition, the concentration-limiting toxicity of oxaliplatin is reduced in the presence of the carotenoid.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colonic Neoplasms; Cryptoxanthins; Disease Models, Animal; DNA-Binding Proteins; Down-Regulation; Drug Synergism; Female; Gene Expression Regulation, Neoplastic; Humans; Mice; Nuclear Proteins; Organoplatinum Compounds; Oxaliplatin; Protein Isoforms; Tumor Protein p73; Tumor Suppressor Protein p53; Tumor Suppressor Proteins; Xenograft Model Antitumor Assays

We examined the effects of β-cryptoxanthin, a typical carotenoid, on inflammatory periodontitis. β-Cryptoxanthin suppressed lipopolysaccharide (LPS)-induced osteoclast formation in co-cultures of bone marrow cells and osteoblasts. In a mouse model of periodontitis, it suppressed bone resorption in the mandibular alveolar bone in vitro and restored alveolar bone loss induced by LPS in vivo. β-Cryptoxanthin might protect against periodontal disease.

Topics: Animals; Bone Marrow Cells; Bone Resorption; Cryptoxanthins; Disease Models, Animal; Humans; Inflammation; Mice; NIH 3T3 Cells; Osteoblasts; Osteoclasts; Periodontitis; Xanthophylls

Various natural carotenoids were proven to have anticarcinogenic activity. Epidemiological investigations have shown that cancer risk is inversely related to the consumption of green and yellow vegetables and fruits. Since beta-carotene is present in abundance in these vegetables and fruits, it has been investigated extensively as possible cancer preventive agent. However, various carotenoids which co-exist with beta-carotene in vegetables and fruits also have anti-carcinogenic activity. And some of them, such as alpha-carotene, showed higher potency than beta-carotene to suppress experimental carcinogenesis. Thus, we have carried out more extensive studies on cancer preventive activities of natural carotenoids in foods; i.e., lutein, lycopene, zeaxanthin and beta-cryptoxanthin. Analysis of the action mechanism of these natural carotenoids is now in progress, and some interesting results have already obtained; for example, beta-cryptoxanthin was suggested to stimulate the expression of RB gene, an anti-oncogene, and p73 gene, which is known as one of the p53-related genes. Based on these results, multi-carotenoids (mixture of natural carotenoids) seems to be of interest to evaluate its usefulness for practice in human cancer prevention.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; beta Carotene; Carotenoids; Colonic Neoplasms; Cryptoxanthins; Disease Models, Animal; Fruit; Humans; Lutein; Lycopene; Methylnitrosourea; Mice; Rats; Rats, Inbred F344; Skin Neoplasms; Tetradecanoylphorbol Acetate; Vegetables; Xanthophylls; Zeaxanthins