• DPPIV
• INSR
• SEMA3E
• caspase 1
• insulin resistance
• natural molecules

• I34I19007170007 European Union - POR MARCHE FESR 2014/2020 - Marche BioBank

• apoptosis
• beetroot
• breast cancer cells
• digestion and absorption
• young shoots

• 2016/23/N/NZ9/01578 National Science Center

• ROS
• apoptosis
• bioactive
• cancer
• chemoprevention
• chemotherapy
• cruciferous vegetables
• curcumin
• nanoformulation
• oncogene
• phytochemicals
• probiotics

• beetroot
• betanin
• biological activity
• health benefits
• nitrate

• SIRT6
• fatty acid
• modulators
• natural products
• peptides
• polyphenols and flavonoids

• Aging/drug effects
• Alzheimer Disease/drug therapy
• Animals
• Biological Products/pharmacology
• Biological Products/therapeutic use
• Diabetes Mellitus/drug therapy
• Histone Deacetylase Inhibitors/pharmacology
• Histone Deacetylase Inhibitors/therapeutic use
• Humans
• Neoplasms/drug therapy
• Sirtuins/antagonists & inhibitors
• Sirtuins/metabolism

• Beetroot
• Betacyanin
• Betanin
• Betaxanthin
• Cancer

Reactive oxygen species (ROS) are produced constantly inside the cells as a consequence of nutrient catabolism. The balance between ROS production and elimination allows to maintain cell redox homeostasis and biological functions, avoiding the occurrence of oxidative distress causing irreversible oxidative damages. A fundamental player in this fine balance is reduced glutathione (GSH), required for the scavenging of ROS as well as of the reactive 2-oxoaldehydes methylglyoxal (MGO). MGO is a cytotoxic compound formed constitutively as byproduct of nutrient catabolism, and in particular of glycolysis, detoxified in a GSH-dependent manner by the glyoxalase pathway consisting in glyoxalase I and glyoxalase II reactions. A physiological increase in ROS production (oxidative eustress, OxeS) is promptly signaled by the decrease of cellular GSH/GSSG ratio which can induce the reversible S-glutathionylation of key proteins aimed at restoring the redox balance. An increase in MGO level also occurs under oxidative stress (OxS) conditions probably due to several events among which the decrease in GSH level and/or the bottleneck of glycolysis caused by the reversible S-glutathionylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase. In the present review, it is shown how MGO can play a role as a stress signaling molecule in response to OxeS, contributing to the coordination of cell metabolism with gene expression by the glycation of specific proteins. Moreover, it is highlighted how the products of MGO metabolism, S-D-lactoylglutathione (SLG) and D-lactate, which can be taken up and metabolized by mitochondria, could play important roles in cell response to OxS, contributing to cytosol-mitochondria crosstalk, cytosolic and mitochondrial GSH pools, energy production, and the restoration of the GSH/GSSG ratio. The role for SLG and glyoxalase II in the regulation of protein function through S-glutathionylation under OxS conditions is also discussed. Overall, the data reported here stress the need for further studies aimed at understanding what role the evolutionary-conserved MGO formation and metabolism can play in cell signaling and response to OxS conditions, the aberration of which may importantly contribute to the pathogenesis of diseases associated to elevated OxS.

• S-D-lactoylglutathione
• glutathione
• glutathionylation
• glyoxalase system
• methylglyoxal
• mitochondria
• redox signaling

Anthocyanins, betalains, riboflavin, carotenoids, chlorophylls and caramel are the basic natural food colorants used in modern food manufacture. Betalains, which are composed of red–violet betacyanin and yellow betaxanthins, are water-soluble pigments that color flowers and fruits. Betalains are pigments primarily produced by plants of the order Caryophyllales. Because of their anti-inflammatory, cognitive impairment, anticancer and anti-hepatitis properties, betalains are useful as pharmaceutical agents and dietary supplements. Betalains also exhibit antimicrobial and antimalarial effects, and as an example, betalain-rich Amaranthus spinosus displays prominent antimalarial activity. Studies also confirmed the antidiabetic effect of betalains, which reduced glycemia by 40% without causing weight loss or liver impairment. These findings show that betalain colorants may be a promising alternative to the synthetic dyes currently used as food additives.

• Beta vulgaris
• beetroot
• betalain
• cancer
• natural product

• antioxidant
• lipid peroxidation
• oxidative stress
• reactive oxygen species
• vitexin

• Anti-tumor effect
• Chinese herbal medicines
• Liposomes
• Targeting strategies
• Tumor microenvironment

• Animals
• Antineoplastic Agents, Phytogenic/administration & dosage
• Drugs, Chinese Herbal/administration & dosage
• Humans
• Liposomes
• Medicine, Chinese Traditional
• Neoplasms/drug therapy
• Phytotherapy
• Tumor Microenvironment/drug effects

• U54 CA198999 NCI NIH HHS

Brazilian red propolis has been proposed as a new source of compounds with cytotoxic activity. Red propolis is a resinous material of vegetal origin, synthesized from the bees of the Appis mellifera family, with recognized biological properties. To obtain actives of low polarity and high cytotoxic profile from red propolis, in this work, we proposed a new solvent accelerated extraction method. A complete 2³ factorial design was carried out to evaluate the influence of the independent variables or factors (e.g., temperature, number of cycles, and extraction time) on the dependent variable or response (i.e., yield of production). The extracts were analyzed by gas chromatography coupled with mass spectrometry for the identification of chemical compounds. Gas chromatography analysis revealed the presence of hydrocarbons, alcohols, ketones, ethers, and terpenes, such as lupeol, lupenone, and lupeol acetate, in most of the obtained extracts. To evaluate the cytotoxicity profile of the obtained bioactives, the 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide colorimetric assay was performed in different tumor cell lines (HCT116 and PC3). The results show that the extract obtained from 70 °C and one cycle of extraction of 10 min exhibited the highest cytotoxic activity against the tested cell lines. The highest yield, however, did not indicate the highest cytotoxic activity, but the optimal extraction conditions were indeed dependent on the temperature (i.e., 70 °C).

• antitumor activity
• extraction
• red propolis
• supercritical liquids

• Alcohols/analysis
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/toxicity
• Cell Line, Tumor
• Ethers/analysis
• Humans
• Ketones/analysis
• Propolis/chemistry
• Propolis/toxicity
• Terpenes/analysis

• CAPES Coordination for Improvement of Higher Education Personnel
• FAPITEC Foundation for Support to Research and Technological Innovation of Sergipe
• M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020 (strategic fund) Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC)

• flavonoid C-glycosides
• food components
• gut microbiota
• protective effects
• vitexin

Background and objectives: Vitexin is a natural flavonoid glycoside mainly extracted from the leaves of vitex, which has a variety of physiological activities. For example, vitexin has antitumor and anti-inflammation activities, and it can also promote blood circulation in the body. However, the function and mechanism of vitexin in nasopharyngeal carcinoma (NPC) are still unclear.

Materials and methods: Cell Counting Kit-8 assay and cell cycle analysis were performed to examine cell survival in response to vitexin. Immunoblotting was used to analyze relative proteins’ expression. NPC xenograft models were established to assess the effect of vitexin in vivo. The luciferase activity of pNFκB-Luc was analyzed by using Dual-Luciferase Reporter Assay System. Quantitative real-time polymerase chain reaction was performed to detect relative genes’ expression. Kinase activity of IKKβ was analyzed in a cell-free system.

Results: In this study, vitexin was found to display significant antitumor activity in NPC in vitro and in vivo. In NPC cells, vitexin inhibited cell cycle progression in NPC cells and induced the cleavages of PARP and inhibited antiapoptotic proteins’ expression, including Bcl-2 and Mcl1. Further studies indicated that vitexin significantly suppressed the luciferase activity of pNF-κB-Luc and inhibited the activation of NF-κB key regulators, including p65, IκBα and IKKs in NPC cells. Moreover, the kinase activity of IKKβ could be suppressed by vitexin in a cell-free system, and overexpression of CA-IKKβ could attenuate the inhibitory effect of vitexin on p65 phosphorylation.

Conclusion: These results indicated that vitexin displayed antitumor activity by suppressing NF-κB signaling in NPC, which suggested that vitexin could be as a potential drug for the treatment of NPC in the future.

• NF-κB
• cell apoptosis
• nasopharyngeal carcinoma
• target
• vitexin

Avenanthramides inhibit proliferation of CaCo-2 and Hep3B cancer cells through induction of apoptosis and downregulation of pro-survival mechanisms.

• C-glycosyl flavonoids
• anticancer
• antiinflammatory
• antioxidant
• betalains
• vitexin-2-O-xyloside

To investigate the effects of berberine on esophageal cancer (EC) cells and its molecular mechanisms.

Human esophageal squamous cell carcinoma cell line KYSE-70 and esophageal adenocarcinoma cell line SKGT4 were used. The effects of berberine on cell proliferation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. For cell cycle progression, KYSE-70 cells were stained with propidium iodide (PI) staining buffer (10 mg/mL PI and 100 mg/mL RNase A) for 30 min and cell cycle was analyzed using a BD FACSCalibur flow cytometer. For apoptosis assay, cells were stained with an Annexin V-FITC/PI apoptosis detection kit. The rate of apoptotic cells was analyzed using a dual laser flow cytometer and estimated using BD ModFit software. Levels of proteins related to cell cycle and apoptosis were examined by western blotting.

Berberine treatment resulted in growth inhibition of KYSE-70 and SKGT4 cells in a dose-dependent and time-dependent manner. KYSE-70 cells were more susceptible to the inhibitory activities of berberine than SKGT4 cells were. In KYSE-70 cells treated with 50 μmol/L berberine for 48 h, the number of cells in G₂/M phase (25.94% ± 5.01%) was significantly higher than that in the control group (9.77% ± 1.28%, P < 0.01), and berberine treatment resulted in p21 up-regulation in KYSE-70 cells. Flow cytometric analyses showed that berberine significantly augmented the KYSE-70 apoptotic population at 12 and 24 h post-treatment, when compared with control cells (0.83% vs 43.78% at 12 h, P < 0.05; 0.15% vs 81.86% at 24 h, P < 0.01), and berberine-induced apoptotic effect was stronger at 24 h compared with 12 h. Western blotting showed that berberine inhibited the phosphorylation of Akt, mammalian target of rapamycin and p70S6K, and enhanced AMP-activated protein kinase phosphorylation in a sustained manner.

Berberine is an inhibitor of human EC cell growth and could be considered as a potential drug for the treatment of EC patients.

• Berberine
• Esophageal cancer
• Antitumor activity
• Proliferation
• Cell cycle
• Apoptosis

• AMP-Activated Protein Kinases/metabolism
• Adenocarcinoma/drug therapy
• Adenocarcinoma/metabolism
• Adenocarcinoma/pathology
• Antineoplastic Agents, Phytogenic/pharmacology
• Apoptosis/drug effects
• Apoptosis Regulatory Proteins/metabolism
• Berberine/pharmacology
• Carcinoma, Squamous Cell/drug therapy
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/pathology
• Cell Cycle Proteins/metabolism
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Dose-Response Relationship, Drug
• Esophageal Neoplasms/drug therapy
• Esophageal Neoplasms/metabolism
• Esophageal Neoplasms/pathology
• Esophageal Squamous Cell Carcinoma
• G2 Phase Cell Cycle Checkpoints/drug effects
• Humans
• Phosphorylation
• Proto-Oncogene Proteins c-akt/metabolism
• Ribosomal Protein S6 Kinases, 70-kDa/metabolism
• TOR Serine-Threonine Kinases/metabolism
• Time Factors