Carotenoids in Cancer Metastasis-Status Quo and Outlook.

Metastasis represents a major obstacle in cancer treatment and the leading cause of cancer-related deaths. Therefore, the identification of compounds targeting the multi-step and complex process of metastasis could improve outcomes in the management of cancer patients. Carotenoids are naturally occurring pigments with a plethora of biological activities. Carotenoids exert a potent anti-cancer capacity in various cancer models in vitro and in vivo, mediated by the modulation of signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of the epithelial-mesenchymal transition and regulatory molecules, such as matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), urokinase plasminogen activator (uPA) and its receptor (uPAR), hypoxia-inducible factor-1α (HIF-1α), and others. Moreover, carotenoids modulate the expression of genes associated with cancer progression and inflammatory processes as key mediators of the complex process involved in metastasis. Nevertheless, due to the predominantly preclinical nature of the known anti-tumor effects of carotenoids, and unclear results from certain carotenoids in specific cancer types and/or specific parts of the population, a precise analysis of the anti-cancer effects of carotenoids is essential. The identification of carotenoids as effective compounds targeting the complex process of cancer progression could improve the outcomes of advanced cancer patients.

Potential Application of Hippophae Rhamnoides in Wheat Bread Production.

Sea buckthorn (Hippophae rhamnoides) berries are well known for their content in bioactive compounds, high acidity, bright yellow color, pleasant taste and odor, thus their addition in a basic food such as bread could be an opportunity for modern food producers. The aim of the present research was to investigate the characteristics and the effects of the berry' flour added in wheat bread (in concentration of 1%, 3% and 5%) on sensory, physicochemical and antioxidant properties, and also bread shelf life. Berry flour contained total polyphenols-1467 mg gallic acid equivalents (GAE)/100 g, of which flavonoids-555 mg GAE/100 g, cinnamic acids-425 mg caffeic acid equivalents (CAE)/100 g, flavonols-668 mg quercetin equivalents (QE)/100 g. The main identified phenolics were catechin, hyperoside, chlorogenic acid, cis- and trans-resveratrol, ferulic and protocatechuic acids, procyanidins B1 and B2, epicatechin, gallic acid, quercetin, p- and m-hydroxybenzoic acids. The antioxidant activity was 7.64 mmol TE/100 g, and carotenoids content 34.93 ± 1.3 mg/100 g. The addition of berry flour increased the antioxidant activity of bread and the shelf life up to 120 h by inhibiting the development of rope spoilage. The obtained results recommend the addition of 1% Hippophae rhamnoides berry flour in wheat bread, in order to obtain a product enriched in health-promoting biomolecules, with better sensorial and antioxidant properties and longer shelf life.

Marine Algae of the Genus Gracilaria as Multi Products Source for Different Biotechnological and Medical Applications.

BACKGROUND: Gracilaria has been shown to be an important source of marine bioactive natural biomaterials and compounds. Although there are no enough patents used Gracilaria worldwide, the current study tries to put the Gracilaria on the spot for further important patents in the future. OBJECTIVE: The current study investigates the pharmaceuticals and biochemical activity of Gracilaria because no previous studies have been carried out to examine the biochemical and pharmaceutical activates of Gracilaria from the Suez Canal of Egypt as an excellent source for bioactive compounds. METHODS: Different advanced experimental models and analytical techniques, such as cytotoxicity, total antioxidant capacity, anticancer, and anti-inflammatory profiling were applied. The phytochemical analysis of different constituents was also carried out. RESULTS: The mineral analysis revealed the presence of copper (188.3 ppm) and iron (10.07 ppm) in addition to a remarkable wealth of selenium and sulfur contents giving up to 36% of its dry mass. The elemental analysis showed high contents of sulfur and nitrogen compounds. The GCMS profiling showed varieties of different bioactive compounds, such as fatty acids, different types of carotenoids in addition to pigments, alkaloids, steroids. Many other compounds, such as carbohydrates and amino acids having antioxidant, anti-inflammatory, and antiviral activities, etc. were identified. The cytotoxicity activity of Gracilaria marine extract was very effective against cancerous cell lines and showed high ability as a potent antitumor due to their bioactive constituents. Specialized screening assays using two anticancer experimental models, i.e., PTK and SKH1 revealed 77.88% and 84.50% inhibition anticancer activity; respectively. The anti-inflammatory activities investigated using four different experimental models, i.e., COX1, COX2, IL6, and TNF resulted in 68%, 81.76%, 56.02% and 78.43% inhibition; respectively. Moreover, Gracilaria extracts showed potent anti-Alzheimer with all concentrations. CONCLUSION: Gracilaria proved to be a multi-product source of marine natural products for different biotechnological applications. Our recommendation is to investigate the Gracilaria bioactive secondary metabolites in order to create and innovate in more patents from current important seaweeds (Gracilaria).

Carotenoids: From Plants to Food and Feed Industries.

In this review, carotenoids from plants are described, and their natural existence is addressed. Carotenoids are 40-carbon isoprenoid molecules that produce the red, yellow, and orange pigmentation found in nature. Various plants, microalgae, bacteria, and fungi are natural sources of carotenoids and are presented in detail. The chemistry of carotenoids and their classification is also described along with the effect of carotenoids on human health which is explained with focus on lutein-zeaxanthin, astaxanthin, canthaxanthin, capsanthin, and lycopene. Clinical studies suggest that carotenoid consumption is associated with lower risk of cardiovascular disease, cancer, and eye disease. Finally, another issue discussed is the role of carotenoids in animals and their feed with focus on birds, fish and crustaceans, livestock, and poultry.

Nutraceutical potentialities of Tunisian Argan oil based on its physicochemical properties and fatty acid content as assessed through Bayesian network analyses.

BACKGROUND: Argan oil is traditionally produced by cold pressing in South-western Morocco where rural population uses it as edible oil as well as for its therapeutic properties which give them in counterpart valuable income. Given the economical interest of this oil, several attempts of fraudulency have been registered in the world global market leading to loss of authenticity. Our purpose is to launch a program of Tunisian Argan oil valorization since trees from this species have been introduced sixty years ago in Tunisia. The first step was thus to characterize the physicochemical properties and determine the chemical composition of Tunisian Argan oil in order to assess its quality. METHODS: Physicochemical parameters of oil quality were determined according to the international standard protocols. Fatty acid content analysis of Argan oils was performed by gas chromatography coupled to mass spectrophotometry. A comparative study was realized among Tunisian, Moroccan and Algerian samples differing also by their extraction procedure. The impact of geographical localisation on the fatty acids composition was studied by statistical and modeling Bayesian analyses. RESULTS: Physicochemical parameters analysis showed interestingly that Tunisian Argan oil could be classified as extra virgin oil. Argan oil is mainly composed by unsaturated fatty acids (80%), mainly oleic and linoleic acid (linoleic acid was positively influenced by the geographical localization (r = 0.899, p = 0.038) and the P/S index (r = 0.987, p = 0.002)) followed by saturated fatty acids (20%) with other beneficial compounds from the unsaponifiable fraction like polyphenols and carotenoids. Together with fatty acid content, these minor components are likely to be responsible for its nutraceutical properties and beneficial effects. CONCLUSION: Tunisian Argan oil displayed valuable qualitative parameters proving its competitiveness in comparison with Moroccan and Algerian oils, and could be therefore considered as extra virgin edible oil for nutraceutical purposes as well as for cosmetic use.

Phytochemical Composition and Antioxidant Capacity of Seven Saskatoon Berry (Amelanchier alnifolia Nutt.) Genotypes Grown in Poland.

The basic chemical composition, bioactive compounds, and antioxidant capacity of fruits of three new Polish breeding clones (No. 5/6, type S, and type N) and four Canadian cultivars (cvs.) ("Martin", "Smoky", "Pembina", and "Honeywood") grown in Poland in 2016 were investigated. Fruits were analyzed for their contents of triterpenoids, carotenoids, chlorophylls, and polyphenolics with the ultra-performance liquid chromatography photodiode detector-quadrupole/time-of-flight mass spectrometry (UPLC-PDA-Q/TOF-MS) method, sugar with the high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) method, and antioxidant capacity with the ability to reduce free radical (ABTS) and ferric reducing ability of plasma (FRAP) method. Thirty-eight bioactive compounds, including twenty-eight polyphenolic compounds (four anthocyanins, nine phenolic acids, nine flavonols, and seven flavan-3-ols), four carotenoids, two chlorophylls, and three triterpenoids were identified in the fruits. The fruits of the tested Saskatoon berry genotypes were found to be rich in phenolic compounds (3773.94-6390.36 mg/100 g·dm), triterpenoids (66.55-91.31 mg/kg·dm), and carotenoids (478.62-561.57 mg/kg·dm), with high ABTS and FRAP capacity (10.38-34.49 and 9.66-25.34 mmol·Trolox/100 g·dm, respectively). Additionally, the berries of these genotypes seemed to be a good source of sugar (9.02-19.69 g/100 g), pectins (0.67%-1.33%), and ash (0.59%-0.67%). Some genotypes of Saskatoon berry, especially the clones type S, type N, and cvs. "Honeywood" and "Smoky", may be selected for their potential applications in commercial cultivation to produce fruits with valuable health-promoting nutritional effects on human health. Additionally, three new genotypes that may offer new functional materials can be recommended for fruit growers.

Carotenoids Database: structures, chemical fingerprints and distribution among organisms.

To promote understanding of how organisms are related via carotenoids, either evolutionarily or symbiotically, or in food chains through natural histories, we built the Carotenoids Database. This provides chemical information on 1117 natural carotenoids with 683 source organisms. For extracting organisms closely related through the biosynthesis of carotenoids, we offer a new similarity search system 'Search similar carotenoids' using our original chemical fingerprint 'Carotenoid DB Chemical Fingerprints'. These Carotenoid DB Chemical Fingerprints describe the chemical substructure and the modification details based upon International Union of Pure and Applied Chemistry (IUPAC) semi-systematic names of the carotenoids. The fingerprints also allow (i) easier prediction of six biological functions of carotenoids: provitamin A, membrane stabilizers, odorous substances, allelochemicals, antiproliferative activity and reverse MDR activity against cancer cells, (ii) easier classification of carotenoid structures, (iii) partial and exact structure searching and (iv) easier extraction of structural isomers and stereoisomers. We believe this to be the first attempt to establish fingerprints using the IUPAC semi-systematic names. For extracting close profiled organisms, we provide a new tool 'Search similar profiled organisms'. Our current statistics show some insights into natural history: carotenoids seem to have been spread largely by bacteria, as they produce C30, C40, C45 and C50 carotenoids, with the widest range of end groups, and they share a small portion of C40 carotenoids with eukaryotes. Archaea share an even smaller portion with eukaryotes. Eukaryotes then have evolved a considerable variety of C40 carotenoids. Considering carotenoids, eukaryotes seem more closely related to bacteria than to archaea aside from 16S rRNA lineage analysis. Database URL: : http://carotenoiddb.jp.

Cancer chemoprevention by natural carotenoids as an efficient strategy.

The use of specific compounds to suppress the growth of tumors or reverse carcinogenesis is defined as chemoprevention. Natural products have been known as one of the most important resources of anticancer agents. Among them, carotenoids are lipophilic molecules accumulating in lipophilic compartments including lipoproteins and/or membranes. Various carotenoids were used as major phytonutrients to inhibit the development of tumors in vitro and in vivo. They have shown different functions such as scavenging free radicals, inhibition of angiogenesis, prevention of cell propagation, and apoptosis induction in lung, colon, breast and prostate. Regarding these roles, most carotenoids possess anti-oxidant properties. However, their therapeutic use is problematic due to the lack of solubility of carotenoids in water. Hence, recent studies have been focused on uncommon carotenoids soluble in water because of their glycosylated form, such as crocin(s) extracted from saffron. These structures with their cytotoxicity effects on human cancer cells are suggested as the most suitable compounds for cancer treatment. Herein, we summarize different functions of carotenoids for suppressing tumor growth.

Optimization of clean extraction methods to isolate carotenoids from the microalga Neochloris oleoabundans and subsequent chemical characterization using liquid chromatography tandem mass spectrometry.

A novel experimental design was used to optimize the extraction of carotenoids from Neochloris oleoabundans using pressurized liquid extraction with food-grade solvents such as ethanol and limonene. Experimental factors, including the extraction temperature and the solvent composition, were optimized using a three-level factorial design. The response variables extraction yield and total amount of carotenoids were assessed. The statistical analysis of the results provided mathematical models to predict the behavior of the responses as a function of the factors involved in the process. The optimum conditions predicted by the model developed in this study were 112 °C as the extraction temperature and 100% ethanol as the extraction solvent. Chemical characterization of the extracts obtained was performed by means of high-performance liquid chromatography-tandem mass spectrometry. The results obtained demonstrated that, under certain growth conditions (photoautotrophically cultured in a medium supplemented with 0.3 g L(-1) KNO3), N. oleoabundans accumulated significant total amounts of the carotenoids (from 57.4 to 120.2 mg carotenoids per gram of extract depending on the extraction conditions), mainly lutein, cantaxanthin, zeaxanthin, and astaxanthin monoesters and diesters.

Carotenoid composition and antioxidant activity of the raw and boiled fruit mesocarp of six varieties of Bactris gasipaes.

Total carotenoid content and composition of carotenoids of six varieties of Bactris gasipaes were determined by spectrophotometry and HPLC, with photodiode array detector. Significant differences in total carotenoid content (1.1 to 22.3 mg/100g) were detected among these varieties. Boiling the fruits for 30 minutes did not affect total carotenoid content, but did change the amount of some specific carotenoids, mainly by the production of Z-isomers. Peach palm varieties had the same carotenoids, but in different proportions, presenting mainly, all E-beta-carotene (26.2% to 47.9%), Z-gamma-carotene (18.2% to 34.3%) and Z-lycopene (10.2% to 26.8%). When antioxidant activity was evaluated using DPPH, it was observed that the variety with higher percentages of beta-carotene (54.1%) presented the higher activity. This is one of the first reports in carotenoid content and antioxidant activity in well typified varieties of Bactris gasipaes, whose results could have a positive impact in the consumption of certain peach palm varieties.

Nucleótidos y carotenoides naturales / Nucleotides and carotenoids

El concepto de los nucleótidos no es nuevo; máxime que son elementos que hacen parte de los componentes naturales de la leche materna. Casi todos los estudios señalan que el consumo de carotenoides, previenen el desarrollo de enfermedades crónicas en la edad adulta, posiblemente por su efecto antioxidante que disminuye el estrés oxidativo, mejorando enfermedades degenerativas y malignas.

The concept of nucleotides is not new, especially since they are elements that are part of the natural components of human milk. Most studies indicate that the consumption of carotenoids, prevent the development of chronic diseases in adulthood, possibly by its antioxidant effect that reduces oxidative stress, improving degenerative diseases and malignancies.

Dietary intake of carotenoids and retinol and endometrial cancer risk in an Italian case-control study.

OBJECTIVES: To provide information on the relation between intake of carotenoids and retinol and endometrial cancer, since available data are inconsistent. Further, carotenoids other than beta-carotene have been rarely investigated. METHODS: We conducted a multi-centric case-control study in various areas of Italy between 1992 and 2006 on 454 women with incident, histologically confirmed endometrial cancer and 908 controls admitted to the same network of hospitals of cases for acute, non-neoplastic conditions. Intake of carotenoids and retinol was computed from a validated and reproducible food frequency questionnaire. We adjusted for selected covariates, including energy intake, and calculated multivariate odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression. RESULTS: Comparing the highest to the lowest quartile of intake, the ORs of endometrial cancer were 0.69 (95% CI, 0.48-0.99) for beta-carotene, 0.65 (95% CI, 0.45-0.94) for beta-cryptoxanthin, and 0.59 (95% CI, 0.41-0.85) for lutein plus zeaxanthin intake. No association emerged with retinol (OR = 1.31, 95% CI, 0.94-1.84), alpha-carotene (OR = 0.94, 95% CI, 0.66-1.34), and lycopene (OR = 0.95, 95% CI, 0.68-1.34). CONCLUSIONS: Our results support a favorable role of selected dietary carotenoids on endometrial cancer risk.

Sphingomonas astaxanthinifaciens sp. nov., a novel astaxanthin-producing bacterium of the family Sphingomonadaceae isolated from Misasa, Tottori, Japan.

A red-pigmented, Gram-negative, motile, strictly aerobic, mesophilic, oval- or short rod-shaped bacterium (TDMA-17(T)) was isolated from fresh water collected at Misasa, a radioactive site in Japan. TDMA-17(T) was slightly tolerant against gamma-ray irradiation, and effectively produced carotenoids (2.8 mg g(-1) dry cells) including, astaxanthin and astaxanthin isomers. Phylogenetic analysis based on 16S rRNA gene sequences placed TDMA-17(T) in a distinct lineage in the family Sphingomonadaceae, and the highest degree of sequence similarity determined were to Sphingomonas aerolata NW12(T) (94.5%), Sphingomonas aurantiaca MA101b(T) (94.0%), Sphingomonas melonis DAPP-PG 224(T) (94.0%), Sphingomonas asaccharolytica IFO 15499(T) (93.9%) and Sphingomonas abaci C42(T) (93.9%). The major fatty acids were C(17 : 1)omega6c (33.0%) and C(18 : 1)omega7c (20.8%). The DNA G+C content was 67.7 mol%. The presence of Q-10 as the main ubiquinone, the presence of Sphingomonadaceae-specific sphingoglycolipid in the polar lipid profiles, the presence of 2-hydroxy fatty acids and the absence of 3-hydroxy fatty acids supported the identification of this strain as a member of the genus Sphingomonas sensu stricto. Phylogenetic distinctiveness and unique phenotypic characteristics differentiated strain TDMA-17(T) from the closely related Sphingomonas species. The results of polyphasic taxonomic analyses suggested that TDMA-17(T) represents a novel Sphingomonas species, for which the name Sphingomonas astaxanthinifaciens sp. nov. is proposed. The type strain is TDMA-17(T) (=NBRC 102146=CCUG 53608).

Some dietary and adipose tissue carotenoids are associated with the risk of nonfatal acute myocardial infarction in Costa Rica.

Antioxidants, particularly carotenoids and tocopherols, may protect against cardiovascular disease. The objective of this study was to determine whether dietary and adipose tissue carotenoids and tocopherols are associated with the risk of myocardial infarction (MI). Cases (n = 1456) of a first acute MI were identified and matched by age, sex, and residence to randomly selected population controls (n = 1456) living in Costa Rica. Carotenoids and tocopherols were measured in adipose tissue using HPLC. Dietary intake was assessed using a validated FFQ. Anthropometrical and lifestyle data were collected using an interviewer-administered questionnaire. Subjects were distributed into quintiles of intake or adipose tissue concentration of carotenoids or tocopherols. The lowest quintile was used as the referent in conditional logistic regression analyses. Adipose tissue beta-carotene showed a significant inverse relation with MI risk; the odds ratio (OR) comparing the highest to the lowest quintile was 0.70 (95% CI: 0.51-0.96, P for trend = 0.02). Intake of fruits and vegetables that are rich in beta-carotene was also inversely associated with the risk of MI (OR = 0.74; CI: 0.54-1.01, P for trend = 0.09). In contrast, lutein + zeaxanthin in adipose tissue (OR = 1.46; CI: 1.05-2.05, P for trend = 0.02) and diet (OR = 1.18; CI: 0.88-1.57, P for trend = 0.02) was positively associated with MI risk. MI risk was not associated with any of the other carotenoids or tocopherols in the diet or adipose tissue. Thus, the inverse association between beta-carotene and MI risk suggests that beta-carotene protects against MI or it is a marker of some protective factor in foods containing beta-carotene. The mechanism underlying the positive association between lutein + zeaxanthin and the risk of MI warrants investigation.

Intake of specific carotenoids and lung cancer risk.

Using newly available food composition data for carotenoids, the authors reanalyzed a population-based case-control study of diet and lung cancer conducted in Hawaii in 1983-1985 (L. Le Marchand et al., J. Natl. Cancer Inst., 81: 1158-1164, 1989). The analysis included interviews with 230 men and 102 women with lung cancer and 597 men and 268 women as controls, frequency-matched to the patients by age and sex. A previously validated quantitative diet history assessed the usual intake of foods rich in carotenoids. After adjusting for smoking and other covariates, no association was found with lung cancer risk for dietary lycopene or beta-cryptoxanthin intake, whereas dose-dependent inverse associations of comparable magnitude were found for dietary beta-carotene, alpha-carotene, and lutein. When subjects were cross-classified by their joint intakes of the latter three carotenoids, those who had a high intake (> median) for all three had the lowest risk for lung cancer. In a similar two-way interaction analysis, the previously reported inverse association of lung cancer with vegetable consumption in these data was found to be stronger than that with intake of these three carotenoids. Consistent with our previous findings, this analysis provides further evidence for a protective effect of certain carotenoids against lung cancer and for the greater protection afforded by consuming a variety of vegetables compared to only foods rich in a particular carotenoid.