Antioxidant capacity and cytotoxic effect of an optimized extract of isabella grape (Vitis labrusca) on breast cancer cells.

The phenolic profile of Isabella grape (Vitis labrusca) offers beneficial properties to human health and makes it a functional food product. In order to better understand the phenolic compounds found in this grape variety and the biological effect they induce on breast cancer cells, an ultrasound-assisted extraction was carried out. During the extraction of polyphenols from Isabella grapes organically grown in Antioquia (Colombia), parameters such as frequency (33 kHz and 40 kHz), time and solvent were optimized to finally obtain a crude extract with antioxidant properties (Oxygen Radical Absorbance Capacity, ORAC: 293.22 ± 34.73 µmol of Trolox/g of sample), associated with a total polyphenol content (TPC) of 43.14 ± 5.00 mg GAE/g sample and a total anthocyanin content composed of 17.69 ± 2.59 mg of malvidin-3-glucoside/100 g of sample. MCF-7 breast cancer cells were treated with different concentrations of the optimized extract, and results show a decrease in cell viability related to mitochondrial membrane depolarization, ROS increase, and chromatin condensation. To determine the possible death induction mechanism, molecular docking was simulated to predict the molecular interactions between the most abundant phenolic compounds in Isabella grape and the main apoptosis-related proteins. The results obtained from in silico and in vitro experiments were consistent with each other, suggesting that the phenolic compounds found in Isabella grape can be considered potential adjuvant chemopreventive agents for the treatment of breast cancer.

Induction of Apoptosis and Decrease of Autophagy in Colon Cancer Cells by an Extract of Lyophilized Mango Pulp.

Previous studies have indicated that mango fruit has a chemopreventive capacity against colorectal cancer cells. The objective of this research was to evaluate the effect of an aqueous extract of lyophilized mango pulp (LMPE) on colon adenocarcinoma cells (SW480) and their metastatic derivatives (SW620) death and cellular invasion. DNA fragmentation was assessed by TUNEL assay; autophagy and expression of DR4 and Bcl-2 by flow cytometry; the expression of 35 apoptosis-related proteins and of matrix metalloproteinases 7 and 9 by immunodetection; and the invasive capacity of the cells by Boyden chamber. The results showed that LMPE at 30 mg/mL and 48 h of exposure results in DNA fragmentation and apoptosis in SW480 (p < 0.001) and SW620 (p < 0.01) cells. Additionally, LMPE decreased autophagy in the SW480 and SW620 cell lines (p < 0.001), which could sensitize them to the DNA damage generated by LMPE. The LMPE did not modulate the expression of matrix metalloproteinases 7 and 9, nor did it affect cellular invasion processes in the SW480 and SW620 cell lines. In conclusion, LMPE induces apoptosis and decreases autophagy in SW480 and SW620 cells.

Andean berry (Vaccinium meridionale Swartz) juice, in combination with Aspirin, displayed antiproliferative and pro-apoptotic mechanisms in vitro while exhibiting protective effects against AOM-induced colorectal cancer in vivo.

Colorectal cancer (CRC) can be either prevented or alleviated using conventional drugs combined with natural treatments. Andean berry (AB, Vaccinium meridionale Sw.) is an underutilized berry with promising anti-inflammatory and antiproliferative effects that could be used to alleviate CRC markers in combination with Aspirin, a well-known CRC preventive drug. This research aimed to evaluate the impact of Aspirin, AB juice (ABJ), and their mixture on colorectal cancer in vitro and in vivo. The treatments (ABJ: 0, 10, 20, and 30 % v/v; Aspirin: 0, 10, 15, and 20 mM; and their combination) were assessed on SW480 cells to test their antiproliferative and pro-apoptotic effect. To evaluate their chemopreventive and chemoprotective effect in vivo, azoxymethane (AOM, 15 mg/kg BW) was used as a chemical inductor of early-stage colon cancer. Balb/c mice (8 weeks' age) were randomly assigned to five groups (n = 6 mice/group): control (no treatment), positive control (AOM-treated mice), AOM + Aspirin (20 mM: 25 mg/kg BW), AOM + ABJ (30 % v/v), and AOM + Aspirin + ABJ (Aspirin: 25 mg/kg BW; ABJ: 30 % v/v). ABJ contained phenolic compounds such as 3,4-dihydroxybenzoic and gallic acids, morin, and rutin. The mixture showed a strongest antiproliferative effect than their counterparts (+10.39-46.23 %). Except for Aspirin (20 mM), the cells were not able to proliferate based on the cloning efficiency test. The mixture was the most effective treatment arresting the cell cycle and increasing G2/M cell population (p < 0.01). Aspirin and ABJ showed mainly intrinsic and extrinsic-mediated apoptotic processes, while the mixture decreased most pro-apoptotic (cytochrome C, DR4, DR5, TNFRSF1A, Bax, and Bad) and anti-apoptotic proteins (Hsp70, Hsp32, and XIAP) compared to the untreated cells. In silico simulations highlighted the interaction between rutin and catalase as the strongest affinity (-10.30 Kcal/mol). ABJ and the mixture decreased aberrant crypt foci in vivo compared to AOM-only treated mice and protected the colonic and liver architecture, this was latter used as a secondary indicator of AOM-metabolic activity. The chemopreventive approach was more effective, related to a prior regulation of cancer-protective mechanisms in vivo, alleviating the AOM-induced damage. The results indicated that Aspirin and ABJ mixtures exhibit antiproliferative and pro-apoptotic effects in SW480 cells inducing mechanisms linked to extrinsic (TNF and TRAIL-mediated apoptosis) and intrinsic (Bax and cytochrome C modulation) pathways. At in vivo levels, the treatments displayed defensive effects against the AOM-induced damage as observed by macroscopic measurements. However, more in vitro, and in vivo approaches are required to completely fulfill the pro-apoptotic, anti-proliferative, and chemopreventive/chemoprotective effects of ABJ.

Inhibition of Cell Proliferation and Induction of Cell Cycle Arrest in Colon Cancer Cells by Lyophilized Mango (Mangifera indica L.) Pulp Extract.

The present study evaluated the antiproliferative capacity and possible cell death mechanisms of lyophilized mango pulp extract (LMPE), applied to human colon cancer cells (SW480) and their metastasis-derived counterparts (SW620). The total phenolic content of LMPE was estimated by the Folin-Ciocalteu method. Three assays were employed to determine its antioxidant capacity: ferric-reducing antioxidant power, oxygen radical absorbance capacity, and 2,2-diphenyl-1-picrylhydrazyl. Furthermore, the antiproliferative activity of LMPE was assessed by sulforhodamine B, clonogenic, and Ki-67 assays. Flow cytometry was employed to examine the cell cycle, production of intracellular reactive oxygen species (ROS), cell-surface phosphatidylserine, and change in mitochondrial membrane potential. LMPE exhibited a high level of total phenolic content and antioxidant activity. The mean maximal inhibitory concentration values of LMPE at 48 h of exposure were 43 and 29 mg/mL for SW480 and SW620, respectively. In the SW480 and SW620 cell lines, LMPE at 50 mg/mL and 48 h of exposure induced an increase in intracellular ROS, cell cycle arrest in the G2/M phase, and probably, apoptotic processes without mitochondrial depolarization. LMPE had an antiproliferative capacity against the human colorectal cancer cell lines SW480 and SW620. These results highlight the chemopreventive potential of LMPE in colorectal cancer treatments.

Traceability of polyphenols in cocoa during the postharvest and industrialization processes and their biological antioxidant potential.

Noncommunicable diseases, the leading cause of mortality around the world, are responsible for approximately 75% of premature adult deaths (ages 30-69). To tackle this issue, a healthy diet based on functional foods, including cocoa and its derivatives, has been increasingly promoted. The polyphenols present in cocoa have been of interest due to their antioxidant potential and their possible protective role in the context of noncommunicable diseases, such as diabetes and cardiovascular conditions. However, during cocoa postharvest and industrialization, the concentration of these bioactive compounds is reduced, possibly affecting their health-promoting properties. Therefore, this paper reviews in the literature in this field to find the total polyphenol content in cocoa during the postharvest and industrialization processes in order to define concentration ranges as a reference point for future research. In addition, it discusses in vitro and in vivo studies into the biological antioxidant potential of cocoa and its derivatives. This review covers publications in indexed databases from 2010 to 2020, their data were processed and presented here using box plots. As a result, we identified the concentration ranges of polyphenols depending on the type of matrix, treatment and country, as well as their relationship with the main bioactive compounds present in cocoa that are associated with their possible antioxidant biological potential and health-related benefits.

Antiproliferative potential of Andean Berry (Vaccinium meridionale Swartz) juice in combination with Aspirin in human SW480 colon adenocarcinoma cells.

Andean Berry (Vaccinium meridionale Sw.) is a South American fruit rich in phytochemicals with promising anti-cancer properties as co-adjuvants to nonsteroidal anti-inflammatory drugs such as Aspirin. This study aimed to evaluate the antiproliferative potential of Andean Berry Juice (ABJ) in combination with Aspirin in human SW480 colon adenocarcinoma cells. ABJ primarily contained 3,4-dihydroxybenzoic and chlorogenic acids. The combined treatment of ABJ (IC50 : 30.0 ± 0.11%) and Aspirin (IC50 : 20.0 ± 0.57) exhibited a higher (p < .01) antiproliferative effect than each counterpart. Moreover the same mixture displayed a lower reduced glutathione/oxidized glutathione ratio (GSH/GSSG) than the untreated cells. ABJ-Aspirin combination induced late apoptosis stage without stimulating mitochondrial depolarization and prompted phosphatidylserine relocalization. These results emphasize the antiproliferative potential of bioactive compounds from ABJ and Aspirin combinations. PRACTICAL APPLICATIONS: Natural products such as Andean Berry (V. meridionale Sw.) juice (ABJ) contains antioxidant polyphenols that could reduce the need to use non-steroidal anti-inflammatory drugs, currently employed in cancer treatment, to prevent its side effects. The high abundance of polyphenols from this underutilized berry could stimulate the standardization of its production and industrial exploitation to be transformed into suitable food products delivering natural bioactive compounds with potential anti-cancer effects in vitro.

Phenolic compounds of blueberries (Vaccinium spp) as a protective strategy against skin cell damage induced by ROS: A review of antioxidant potential and antiproliferative capacity.

The skin is a tissue with a high metabolic activity that acts as a protective layer for the internal organs of the body. This tissue is exposed to a variety of damaging agents, including reactive oxygen species (ROS), which can lead to oxidative damage to various macromolecules, disrupting vital cellular processes and increasing mutations. A situation referred to as oxidative stress occurs when a large amount of oxidants exceeds the capacity of the antioxidant defense system. Oxidative stress is considered a contributory factor to the aging process and the pathogenesis of various skin diseases, including cancer. Several current studies seek to identify new natural compounds with properties that mitigate the harmful effects of ROS, thereby acting as blockers or suppressors of the carcinogenesis process. This review briefly presents the relationship between ultraviolet radiation, ROS, and skin damage; and summarizes the in vitro and in vivo experimental evidence of the chemopreventive effect on skin cancer of phenolic compounds from blueberries (Vaccinium spp). Although several studies addressed the topic of bioactive compounds and their activities as possible anticancer agents, none have focused on the antioxidative action and antiproliferative effects on skin cancer of phenolic compounds derived from blueberries.

Andean berry (Vaccinium meridionale Swartz) juice in combination with Aspirin modulated anti-inflammatory markers on LPS-stimulated RAW 264.7 macrophages.

V. meridionale Swartz is an underutilized Andean Berry that has been linked to several health benefits potentially derived from its anti-inflammatory effects. This research aimed to evaluate the impact of Andean Berry Juice (ABJ) combined with Aspirin in the modulation of anti-inflammatory markers from LPS-stimulated RAW 264.7 macrophages. The chemical characterization of ABJ showed a high content of polyphenols, mainly gallic acid (659-75 µg/g) and cyanidin chloride (418.61 µg/mL). Compared to LPS-stimulated macrophages, ABJ, Aspirin, and its combination reduced NO and ROS production (3.26-42.55 and 17.59-65.68%, respectively). In comparison, the half inhibitory concentration of NO reduction (IC50) was found at 7.69% v/v (ABJ) and 24.48 mM (Aspirin). Compared to the pro-inflammatory control (LPS), ABJ reduced IL-1ß, MCP-1, and GCSF; Aspirin decreased IL1R1, MCP-1, GMCSF, GCSF, and TNF-α; and the ABJ + Aspirin treatment reduced IL1R, GMCSF, and CXCL10. The in silico interaction of cytokines and the prediction of potential binding interactions suggested CCR1, CCR5, and NF-kB modulation. These results showed the anti-inflammatory potential of underutilized South American berries and their co-adjuvant effect with known drugs such as Aspirin in the resolution of inflammatory-derived conditions. This is the first report of the anti-inflammatory effects of V. meridionale Swartz juice in combination with Aspirin on LPS-challenged RAW 264.7 macrophages.

Free radical scavenging capacity and cytotoxic and antiproliferative effects of Vaccinium meridionale Sw. agains colon cancer cell lines / Capacidad atrapadora de radicales libres, efectos citotóxicos y antiproliferativos de Vaccinium meridionale Sw. en líneas celulares de cáncer de colon

Introduction: Vaccinium meridionale Swartz, of the family Ericaceae, is commonly known as mortiño or agraz. The plant is considered a functional food, with a content of anthocyanins and antioxidants similar to or greater than that reported for other Vaccinium species. However, little is known about its nutraceutical and medicinal properties. Objectives: determine the antioxidant activity and cytotoxic and antiproliferative effect of mortiño fruit aqueous extract against colon adenocarcinoma cells (SW480) and their derived metastatic cells (SW620). Methods: total phenols and anthocyanins were determined by the Folin-Ciocalteu method. Caffeoyl derivatives were determined by HPLC-DAD. Antioxidant activity was analyzed as the ability to scavenge reactive oxygen species (ROS), reactive nitrogen species (RNI), peroxyl radicals and hydroxyl radicals. Cytotoxic and antiproliferative activities were studied by MTT and sulforhodamine B. Results: the following substances were found in 100 g of lyophilized extract: total phenols (2 546 mg GAE), anthocyanins (150.7 mg C3G), chlorogenic acid (126 mg), ferulic acid (108 mg) and coumaric acid (63 mg). Hydroxyl radical scavenging capacity was 36 147.5 ?mol DMSO, whereas ROS and RNS scavenging capacity was 29 255.9 y 41 775.2 ?molTrolox, respectively. ORAC value was 41 775.2 ?molTrolox. A dose-dependent cytotoxic and antiproliferative effect was observed. IC50 value was 59.12 µg/ml for SW480 and 56.10 µg/mL for SW620. Conclusions: mortiño fruit aqueous extract exhibited antioxidant, cytotoxic and antiproliferative activities comparable to those of other berries of the genus Vaccinium, which could be partly explained by the presence of a high content of anthocyanins and phenolic acids.

Introducción: Vaccinium meridionale Swartz, pertenece a la familia Ericaceae, conocida comúnmente como mortiño agraz. Considerado un alimento funcional por su contenido de antocianinas y antioxidantes similares o mayor al reportado para otras especies de Vaccinium. Sin embargo, poco se conoce sobre sus propiedades nutracéuticas y en la salud. Objetivos: determinar en extracto acuoso del fruto mortiño, la actividad antioxidante y su efecto citotóxico y antiproliferativo en células de adenocarcinoma de colon (SW480) y sus derivadas metastásicas (SW620). Métodos: contenido de fenoles y antocianinas totales se determinó por el método Folin-Ciocalteu, los derivados caffeoil por HPLC-DAD. La actividad antioxidante se analizó como habilidad para atrapar especies reactivas del oxígeno (ROS) y del nitrógeno (RNI), radicales peróxilo e hidróxilo. La actividad citotóxica y antiproliferativa se estudiaron por MTT y sulforodamina B. Resultados : en 100 g de liofilizado se encontrófenoles totales (2546 mg GAE), antocianinas (150,7 mg C3G), ácido clorogénico (126 mg), ácido ferúlico (108 mg) y cumárico (63 mg), capacidad atrapadora de radical hidroxilo fue 36147,5 ?mol DMSO, capacidad atrapadorade ROS y RNS fue 29255,9 y 41775,2 ?mol Trolox, respectivamente, valor ORAC 41775,2 ?mol Trolox. Se observó un efecto citotóxico y antiproliferativo dosis-dependiente. El valor IC50 para SW480: 59,12 µg/mL y SW620: 56,10 µg/mL. Conclusiones: el extracto acuoso del fruto del mortiño exhibió actividades antioxidantes, citotóxicas y antiproliferativas comparables a las de otras bayas del género Vaccinium, lo que podría ser explicado parcialmente por la presencia del alto contenido de antocianinas y ácidos fenólicos.

Antioxidant and antiproliferative activity of ethanolic and aqueous extracts from leaves and fruits juice Passiflora edulis / Actividad antioxidante y antiproliferativa de extractos etanólico y acuoso de las hojas y el jugo del fruto de Passiflora edulis

Background: Extracts from a variety of fruit trees have been used for therapeutic applications for preventing oxidative stress associated to chronic diseases. Objective: To investigate the antioxidant and antiproliferative activity of ethanolic and aqueous extracts from leaves and fruits of Passiflora edulis. Materials and methods: A preliminary phytochemical screening was performed; antioxidant activity was evaluated through DPPH assay, the scavenging activity for hydroxyl radical, antihemolytic activity and total phenolic content; cytotoxic and antiproliferative activities were evaluated by MTT and sulforhodamine B assays respectively in colon adenocarcinoma SW480 cells and their metastatic-derived SW620 cells. Results: Phytochemical analyses revealed presence of tannins, flavonoids and cardiotonic glycosides. Ethanolic extract from leaves showed the best antioxidant activity (EC50 = 0.096 mg/ml) in the DPPH assay and the juice (EC50 = 0.022 mg/ml) for the Hydroxyl free radical-scavenging activity. All extracts inhibited more than 98% the hemolysis induced by H2O2. The aqueous extract from leaves showed the highest cytotoxic activity against SW480 and SW620 cells. Conclusions: Findings from this study suggest that P. edulis is a potential source of phytochemical compounds with antioxidant and antiproliferative properties.

Antecedentes: extractos de varios árboles frutales se han utilizado en diferentes aplicaciones terapéuticas para prevenir el estrés oxidativo asociado a enfermedades crónicas. Objetivo: investigar la actividad antioxidante y antiproliferativa de extractos etanólico y acuosos de las hojas y del fruto de Passiflora edulis. Materiales y métodos: se realizó marcha fitoquímica preliminar, la actividad antioxidante se evaluó por DPPH, actividad de remoción de radicales hidroxilo, actividad antihemolítica y contenido fenólico total. En células de adenocarcinoma de colon SW480 y sus derivadas metastásicas SW620 se evaluó la actividad citotóxica y antiproliferativa por el método de MTT y sulforodamina B respectivamente. Resultados: el análisis fitoquímico reveló la presencia de taninos, flavonoides y glicósidos cardiotónicos. El extracto etanólico de las hojas mostró la mayor actividad antioxidante (EC50 = 0,096 mg/ml) por DPPH y el jugo (EC50 = 0,022 mg/ml) para remover el radical hidroxilo. Todos los extractos inhibieron más del 98% la hemólisis inducida por H2O2. El extracto acuoso de las hojas mostró la mayor actividad citotóxica y antiproliferativa contra células SW480 y SW620. Conclusiones: los hallazgos de este estudio sugieren que P. edulis es una fuente potencial de compuestos fitoquímicos con propiedades antioxidante y antiproliferativa.