Antiproliferative, Antioxidant, Chemopreventive and Antiangiogenic Potential of Chromatographic Fractions from Anemonia sulcata with and without Its Symbiont Symbiodinium in Colorectal Cancer Therapy.

Anemonia sulcata may be a source of marine natural products (MNPs) due to the antioxidant and antitumor activity of its crude homogenates shown in vitro in colon cancer cells. A bioguided chromatographic fractionation assay of crude Anemonia sulcata homogenates with and without its symbiont Symbiodinium was performed to characterize their bioactive composition and further determine their biological potential for the management of colorectal cancer (CRC). The 20% fractions retained the in vitro antioxidant activity previously reported for homogenates. As such, activation of antioxidant and detoxifying enzymes was also evaluated. The 40% fractions showed the greatest antiproliferative activity in T84 cells, synergistic effects with 5-fluoruracil and oxaliplatin, overexpression of apoptosis-related proteins, cytotoxicity on tumorspheres, and antiangiogenic activity. The predominantly polar lipids and toxins tentatively identified in the 20% and 40% fractions could be related to their biological activity in colon cancer cells although further characterizations of the active fractions are necessary to isolate and purify the bioactive compounds.

In vitro evidence of the antitumor capacity of Solanaceae and Cucurbitaceae in colon cancer: A systematic review.

Colon cancer is the fourth leading cause of cancer deaths around the world. Despite advances in understanding its etiology and in diagnosis and treatment, new therapeutic strategies are still required. In this sense, the Solanaceae and Cucurbitaceae families have been widely used to treat various pathologies, including cancer, for their bioactive components. The objective of this systematic review was to analyze the antitumor activity of the bioactive components present in extracts from Solanaceae and Cucurbitaceae families using different in in vitro models of colon cancer. 241 publications have been identified (published from January 2008 to January 2020) from different electronic data base. 44 articles were included, 26 of which examined the Solanaceae family. The antitumor activity exhibited by this family was due to the withanolide-type steroid compounds they harbor. 18 articles were related to the Cucurbitaceae family. This family is characterized by their production of cucurbitacin-type triterpenoid compounds and their derivatives, which confer antitumor activity. In conclusion, the different genera belonging to both families are an important source of bioactive compounds with relevant activity against colon cancer. More experimental and in vivo studies will be required to corroborate their antitumor activity and to leverage them in future clinical practice.

In Vivo Nutritional Assessment of the Microalga Nannochloropsis gaditana and Evaluation of the Antioxidant and Antiproliferative Capacity of Its Functional Extracts.

Nannochloropsis gaditana is a microalga with interesting nutritional and functional value due to its high content of protein, polyunsaturated fatty acids, and bioactive compounds. However, the hardness of its cell wall prevents accessibility to these components. This work aimed to study the effect of a treatment to increase the fragility of the cell wall on the bioavailability of its nutrients and functional compounds. The antioxidant and antiproliferative capacity of functional extracts from treated and untreated N. gaditana was assessed, and the profile of bioactive compounds was characterized. Furthermore, to study the effect of treatment on its nutrient availability and functional capacity, an in vivo experiment was carried out using a rat experimental model and a 20% dietary inclusion level of microalgae. Functional extracts from treated N. gaditana exhibited higher antioxidant activity than the untreated control. Furthermore, the treated microalga induced hypoglycemic action, higher nitrogen digestibility, and increased hepatic antioxidant activity. In conclusion, N. gaditana has interesting hepatoprotective, antioxidant, and anti-inflammatory potential, thus proving itself an ideal functional food candidate, especially if the microalga is treated to increase the fragility of its cell wall before consumption.

The combined treatment with lentil protein hydrolysate and a mixed training protocol is an efficient lifestyle intervention to manage cardiovascular and renal alterations in obese Zucker rats.

PURPOSE: Functional and structural changes in cardiovascular and renal systems resulting from obesity and metabolic syndrome represent a severe risk to human health. Lifestyle interventions such as combining healthy diet with adequate physical exercise protocols are good strategies to manage these pathologies. In this research, the effects of lentil protein hydrolysate administration, combined or not with a mixed training protocol, on insulin resistance, cardiovascular and renal functionality were studied in the obese Zucker rat experimental model. METHODS: Thirty-two rats (16 lean and 16 obese subdivided in sedentary and trained animals) were administered lentil protein hydrolysate, whereas another 32 subdivided in the same experimental design were administered placebo. The experiment lasted for 8 weeks. At the end of the experimental period, insulin resistance and different parameters of cardiovascular and renal functionality were measured. RESULTS: The individual or combined interventions with lentil protein hydrolysate and mixed training protocol were efficient at counteracting some of the metabolic, cardiovascular and renal alterations characterizing the obese Zucker rat. Specifically, lentil protein hydrolysate decreased hyperphagia, amplitude of QRS complex, plasma ACE and selectin E expression in aorta, while increasing urinary volume and pH. Exercise showed beneficial actions on HOMA-IR, QRS amplitude, QTc interval, urinary volume, kidney weight and Mn-SOD activity. Interestingly, most of the mentioned benefits of exercise were more consistent when protein hydrolysate was also administered. CONCLUSION: The interesting synergies between the two interventions assessed qualify them as alternative therapeutic strategies to treat cardiovascular and kidney diseases associated to the metabolic syndrome.

Aerobic interval exercise improves renal functionality and affects mineral metabolism in obese Zucker rats.

Obesity, metabolic syndrome, and renal injury are considered risk factors for type 2 diabetes, as well as kidney disease. Functional and structural changes in the kidney as consequence of obesity and metabolic syndrome may lead to impaired mineral metabolism in what is known as chronic kidney disease-mineral and bone disorder. Lifestyle interventions such as physical activity are good strategies to manage these pathologies and therefore, prevent the loss of kidney functionality and related complications in mineral metabolism. In this study, we have used 40 male Zucker rats that were randomly allocated into four different experimental groups, two of them (an obese and a lean one) performed an aerobic interval training protocol, and the other two groups were sedentary. At the end of the experimental period (8 wk), urine, plasma, and femur were collected for biochemical and mineral composition analysis, whereas the kidney was processed for histological studies. The obese rats exhibited albuminuria, glomerulosclerosis, and hypertrophy in glomeruli and renal tubule in some areas, together with alterations in mineral content of plasma but not of femur. The training protocol prevented the generation of albuminuria and glomerulosclerosis, showing a significant action on plasma and bone mineral levels. Therefore, the specific training protocol used in this study was able to prevent the development of diabetic nephropathy and affected the metabolism of certain minerals.

Effects of Hypertrophy Exercise in Bone Turnover Markers and Structure in Growing Male Rats.

The benefits of exercise on bone density, structure and turnover markers are rather controversial. The present study aimed to examine the effects of hypertrophy exercise (HE) on bone. 20 male Wistar rats were randomly distributed in 2 experimental groups, one performing HE and the other untrained over 12 weeks. Plasma parameters, bone mineral content, bone mineral density (BMD), structure, and trabecular and cortical microarchitecture were measured. Femur Mg content was 12% higher (p<0.001), whereas femur length, dry weight, P content, and aminoterminal propeptides of type I procollagen were lower in the HE group (all, p<0.05). Total BMD and cortical/subcortical BMD were higher (both, p<0.01), whereas total cross-sectional and trabecular areas were lower (both, p<0.001), and cortical area and thickness were lower in the HE (both, p<0.05). Trabecular connectivity density, number, mean density of total and bone volume were higher in the HE (all, p<0.05). Cortical volume fraction and the mean density of total volume of the diaphysis were lower, whereas the cortical volume density was higher in the HE (all, p<0.05). This HE protocol may have beneficial effect on cancellous bone microarchitecture, but it induces low bone formation and is associated with hypogonadism in growing male rats. However, this type of training might be inefficient to maintain appropriate cortical thickness.

Effects of interval aerobic training combined with strength exercise on body composition, glycaemic and lipid profile and aerobic capacity of obese rats.

The purpose of this study was to investigate the effects of interval aerobic training combined with strength exercise in the same training session on body composition, and glycaemic and lipid profile in obese rats. Sixteen lean Zucker rats and sixteen obese Zucker rats were randomly divided into exercise and sedentary subgroups (4 groups, n = 8). Exercise consisted of interval aerobic training combined with strength exercise in the same training session. The animals trained 60 min/day, 5 days/week for 8 weeks. Body composition, lipid and glycaemic profiles and inflammatory markers were assessed. Results showed that fat mass was reduced in both lean and obese rats following the exercise training (effect size (95% confidence interval (CI)) = 1.8 (0.5-3.0)). Plasma low-density lipoprotein-cholesterol and fasting glucose were lower in the exercise compared to the sedentary groups (d = 2.0 (0.7-3.2) and 1.8 (0.5-3.0), respectively). Plasma insulin was reduced in exercise compared to sedentary groups (d = 2.1 (0.8-3.4)). Some exercise × phenotype interactions showed that the highest decreases in insulin, homeostatic model assessment-insulin resistance, fasting and postprandial glucose were observed in the obese + exercise group (all, P < 0.01). The findings of this study suggest that interval aerobic training combined with strength exercise would improve body composition, and lipid and glycaemic profiles, especially in obese rats.

Improvement of the antioxidant and hypolipidaemic effects of cowpea flours (Vigna unguiculata) by fermentation: results of in vitro and in vivo experiments.

BACKGROUND: The antioxidant capacity and hypolipidaemic effects of Vigna unguiculata, as well as their potential improvement by different fermentation and thermal processes were studied using in vitro and in vivo methods. RESULTS: Phenolic content and reducing capacity of legume acetone extract were significantly increased by different fermentation processes, and by the thermal treatment of fermented legume flours. TBARS inhibiting capacity was increased by fermentation but not by thermal treatment. A higher ability to decrease Cu(2+)/H2O2-induced electrophoretic mobility of LDL was found in fermented when compared to raw legume extracts, and a higher protective effect on short term metabolic status of HT-29 cells was found for raw and lactobacillus-fermented Vigna followed by naturally fermented Vigna extracts. Significant improvements in plasma antioxidant capacity and hepatic activity of antioxidant enzymes were observed in rats that consumed fermented legume flours when compared to the untreated legume or a casein-methionine control diet. In addition, liver weight and plasma levels of cholesterol and triglycerides were also positively affected by untreated or naturally fermented Vigna. CONCLUSION: V. unguiculata has demonstrated its potential as a functional food with interesting antioxidant and lipid lowering properties, which can be further augmented by fermentation processes associated or not to thermal processing.

Synthesis of [(77)Se]-methylselenocysteine when preparing sauerkraut in the presence of [(77)Se]-selenite. Metabolic transformation of [ (77)Se]-methylselenocysteine in Wistar rats determined by LC-IDA-ICP-MS.

The use of enriched Se isotopes as tracers has provided important information on Se metabolism. However, selenium isotopes are expensive and difficult to obtain. A simple and cheap strategy based on the production of [(77)Se]-methylselenocysteine ([(77)Se]-MeSeCys) when preparing sauerkraut in the presence of [(77)Se]-selenite was developed. The resulting [(77)Se]-MeSeCys was used for evaluating the metabolic transformation of MeSeCys in Wistar rats, by feeding them with an AIN-93 M diet containing 20 % sauerkraut enriched in [(77)Se]-MeSeCys. Organs (liver, kidney, brain, testicles, and heart) were obtained after seven days of treatment and subjected to total selenium and selenium-speciation analysis by high-performance liquid chromatography coupled with isotope-dilution-analysis inductively-coupled-plasma mass spectrometry (HPLC-IDA-ICP-MS). Analysis of (77)Se-labeled organs revealed a prominent increase (more than 100 % Se-level enhancement) of selenium in the kidney and heart, whereas in the liver selenium concentration only increased by up to 20 % and it remained constant in the brain and testicles. (77)Se-enriched-sauerkraut supplementation does not alter the concentration of other essential elements in comparison to controls except for in the heart and kidney, in which selenium was positively correlated with Mg, Zn, Cu, and Mo. HPLC-ICP-MS analysis of hydrolyzed extracts after carbamidomethylation of the (77)Se-labeled organs revealed the presence of [(77)Se]-SeCys and an unknown Se-containing peak, the identity of which could not be verified by electrospray-ionization (ESI)-MS-MS. Low amounts of [(77)Se]-MeSeCys were found in (77)Se-labeled liver and kidney extracts, suggesting the incorporation of this selenium species in its intact form.

A Novel Plant-Based Nutraceutical Combined with Exercise Can Revert Oxidative Status in Plasma and Liver in a Diet-Induced-Obesity Animal Model.

The prevalence of obesity increases alarmingly every year mostly due to external factors such as high-fat and high-refined sugar intake associated with a sedentary lifestyle. It triggers metabolic disorders such as insulin resistance, hyperlipemia, non-alcoholic fatty liver disease, chronic inflammation, oxidative stress, and gut microbiota dysbiosis. The aim of this study was to evaluate the beneficial effects of a combined intervention with caloric restriction, nutraceutical intake, and a mixed training protocol on oxidative stress, inflammation, and gut dysbiosis derived from the development of obesity in a C57BL6/J mouse experimental model of diet-induced obesity (4.6 Kcal/g diet, 45% Kcal as fat, and 20% fructose in the drinking fluid). The nutraceutical was formulated with ethanolic extracts of Argania spinosa pulp (10%) and Camelina sativa seeds (10%) and with protein hydrolysates from Psoralea corylifolia seeds (40%) and Spirodela polyrhiza whole plants (40%). The combination of nutraceutical and exercise decreased the animals' body weights and inflammatory markers (TNFα, IL-6, and resistin) in plasma, while increasing gene expression of cat, sod2, gsta2, and nqo1 in the liver. Obese animals showed lower ß-diversity of microbiota and a higher Firmicutes/Bacteroidetes ratio vs. normocaloric controls that were reversed by all interventions implemented. Dietary inclusion of a nutraceutical with high antioxidant potential combined with an exercise protocol can be beneficial for bodyweight control and improvement of metabolic status in patients undergoing obesity treatment.

Novel insights and mechanisms of diet-induced obesity: Mid-term versus long-term effects on hepatic transcriptome and antioxidant capacity in Sprague-Dawley rats.

AIMS: The study of molecular mechanisms related to obesity and associated pathologies like type 2-diabetes and non-alcoholic fatty liver disease requires animal experimental models in which the type of obesogenic diet and length of the experimental period to induce obesity deeply affect the metabolic alterations. Therefore, this study aimed to test the influence of aging along a rat model of diet-induced obesity in gene expression of the hepatic transcriptome. MAIN METHODS: A high-fat/high-fructose diet to induce obesity was used. Mid- (13 weeks) and long-term (21 weeks) periods were established. Caloric intake, bodyweight, hepatic fat, fatty acid profile, histological changes, antioxidant activity, and complete transcriptome were analyzed. KEY FINDINGS: Excess bodyweight, hepatic steatosis and altered lipid histology, modifications in liver antioxidant activity, and dysregulated expression of transcripts related to cell structure, glucose & lipid metabolism, antioxidant & detoxifying capacity were found. Modifications in obese and control rats were accounted for by the different lengths of the experimental period studied. SIGNIFICANCE: Main mechanisms of hepatic fat accumulation were de novo lipogenesis or altered fatty acid catabolism for mid- or long-term study, respectively. Therefore, the choice of obesity-induction length is a key factor in the model of obesity used as a control for each specific experimental design.

Preventive effects of Brassicaceae family for colon cancer prevention: A focus on in vitro studies.

The emergence of adverse effects and resistance to colorectal cancer (CRC) current therapies calls for the development of new strategies aimed at both preventing and treating. In this context, functional extracts from Brassicaceae family contains abundant bioactive compounds directly related to a positive effect on human health including cancer. The main objective of this systematic review is to compile all recent studies that analyzed the in vitro antiproliferative activity of functional extracts or isolated molecules from the Brassicaceae family against CRC. A total of 711 articles published between January 2011 and May 2021 were identified. Of them, 68 met our inclusion criteria. Different standardized protocols using variable parts of plants of the Brassicaceae family resulted in diverse bioactive extracts and/or compounds. Most of them were related to isothiocyanates, which showed significant antitumor activity against CRC. These in vitro studies provide an excellent guide to direct research on the applications of plants of the Brassicaceae family to the prevention of this type of tumor. The extracts and molecules with demonstrated activity against CRC should be tested in vivo and in clinical trials to determine their usefulness in the prevention of this cancer to reduce its global incidence.

Combination of Caloric Restriction and a Mixed Training Protocol as an Effective Strategy to Counteract the Deleterious Effects in Trabecular Bone Microarchitecture Caused by a Diet-Induced Obesity in Sprague Dawley Rats.

The association of obesity with changes in bone mass is not clear. Obese individuals tend to have an increased bone mineral density, but other studies have shown that obesity is a major risk factor for fractures. The mechanisms of bone response during a weight loss therapy as well as the possible osteoprotective effect of exercise should be analyzed. The aim of this study was to test the effects of a weight-loss program based on the combination of caloric restriction and/or a mixed training protocol on different parameters of bone morphology and functionality in a DIO rat model. Three stages were established over a 21-week period (obesity induction 0-12 w, weight loss intervention 12-15 w, weight maintenance intervention 15-21 w) in 88 male Sprague Dawley rats. Bone microarchitecture, total mineral and elemental composition, and bone metabolism parameters were assessed. Weight loss interventions were associated to healthy changes in body composition, decreasing body fat and increasing lean body mass. On the other hand, obesity was related to a higher content of bone resorption and inflammatory markers, which was decreased by the weight control interventions. Caloric restriction led to marked changes in trabecular microarchitecture, with a significant decrease in total volume but no changes in bone volume (BV). In addition, the intervention diet caused an increase in trabeculae number and a decrease in trabecular spacing. The training protocol increased the pore diameter and reversed the changes in cortical porosity and density of BV induced by the high protein diet at diaphysis level. Regarding the weight-maintenance stage, diminished SMI values indicate the presence of more plate-like spongiosa in sedentary and exercise groups. In conclusion, the lifestyle interventions of caloric restriction and mixed training protocol implemented as weight loss strategies have been effective to counteract some of the deleterious effects caused by a dietary induction of obesity, specifically in trabecular bone morphometric parameters as well as bone mineral content.

Bioavailability and biotransformation of linolenic acid from basil seed oil as a novel source of omega-3 fatty acids tested on a rat experimental model.

Basil is an aromatic herb with a high concentration of bioactive compounds. The oil extracted from its seeds is a good source of α-linolenic acid (ALA) and also provides substantial amounts of linoleic acid (LA). This study aimed to test the bioavailability of the oil derived from basil seeds and its effects on different physiological parameters using 7-15% dietary inclusion levels. Furthermore, the assimilation of LA and ALA and their transformation in long-chain polyunsaturated fatty acids (LC-PUFAs) have been studied. Digestive utilization of total fat from basil seed oil (BSO) was high and similar to that of olive oil used as a control. Consumption of BSO resulted in increased LA and ALA levels of the plasma, liver, and erythrocyte membrane. In addition, the transformation of LA to arachidonic acid (ARA) was decreased by the high dietary intake of ALA which redirected the pathway of the Δ-6 desaturase enzyme towards the transformation of ALA into eicosapentaenoic acid (EPA). No alterations of hematological and plasma biochemical parameters were found for the 7 and 10% dietary inclusion levels of BSO, whereas a decrease in the platelet count and an increase in total- and HDL-cholesterol as well as plasma alkaline phosphatase (ALP) were found for a 15% BSO dose. In conclusion, BSO is a good source of ALA to be transformed into EPA and decrease the precursor of the pro-inflammatory molecule ARA. This effect on the levels of EPA in different tissues offers potential for its use as a dietary supplement, novel functional food, or a constituent of nutraceutical formulations to treat different pathologies.

Colon cancer therapy with calcium phosphate nanoparticles loading bioactive compounds from Euphorbia lathyris: In vitro and in vivo assay.

Amorphous calcium phosphate nanoparticles (ACP NPs) exhibit excellent biocompatibility and biodegradability properties. ACP NPs were functionalized with two coumarin compounds (esculetin and euphorbetin) extracted from Euphorbia lathyris seeds (BC-ACP NPs) showing high loading capacity (0.03% and 0.34% (w/w) for esculetin and euphorbetin, respectively) and adsorption efficiency (2.6% and 33.5%, respectively). BC-ACP NPs, no toxic to human blood cells, showed a more selective cytotoxicity against colorectal cancer (CRC) cells (T-84 cells) (IC50, 71.42 µg/ml) compared to non-tumor (CCD18) cells (IC50, 420.77 µg/ml). Both, the inhibition of carbonic anhydrase and autophagic cell death appeared to be involved in their action mechanism. Interestingly, in vivo treatment with BC-ACPs NPs using two different models of CRC induction showed a significant reduction in tumor volume (62%) and a significant decrease in the number and size of polyps. A poor development of tumor vasculature and invasion of normal tissue were also observed. Moreover, treatment increased the bacterial population of Akkermansia by restoring antioxidant systems in the colonic mucosa of mice. These results show a promising pathway to design innovative and more efficient therapies against CRC based on biomimetic calcium phosphate NPs loaded with natural products.

Antioxidant and Chemopreventive Activity of Protein Hydrolysates from Raw and Germinated Flour of Legumes with Commercial Interest in Colorectal Cancer.

Legumes are a highly nutritious source of plant protein, fiber, minerals and vitamins. However, they also contain several bioactive compounds with significant potential benefits for human health. The objectives of this study were to evaluate the antioxidant, antitumor and chemopreventive activity of functional extracts from legumes using raw and germinated flours of six legume species of commercial interest. The methodology carried out consisted on the development of protein hydrolysates, assessment of their antioxidant capacity and in vitro tests on T84, HCT15 and SW480 colorectal cancer (CRC) cell lines. Our results showed a high antitumor activity of protein hydrolysate from M. sativa. Likewise, when combined with 5-Fluorouracile (5-Fu), there was a synergistic effect using extract concentrations from 50 to 175 µg/mL and 5-Fu concentrations from 1.5 to 5 µM. Similarly, the induction effect on detoxifying enzymes by the extracts of M. sativa, germinated V. faba Baraca × LVzt1 and V. narbonensis, which produced a higher induction rate than the positive control sulforaphane (10 µM), should be highlighted. Therefore, incorporating these enzymes into the diet could provide nutritional effects, as well as play an effective role in cancer chemoprevention and therapy.

Effects of high-whey-protein intake and resistance training on renal, bone and metabolic parameters in rats.

Consumption of high-protein (HP) diets is postulated to exert a negative influence on bone and renal health. However, no conclusive evidence has been presented related to this issue or to the potential protective action of resistance training on HP-induced systemic effects. We examined the effects of HP diet consumption on food intake, body-weight gain, body composition, and renal, bone and metabolic parameters of rats performing resistance training. A total of ninety-six adult male Wistar rats were randomly distributed in twelve experimental groups (n 8): normal-protein (10%) or HP (45%) diets, with or without resistance training, killed for experimental periods of 1, 2 or 3 months. Diets were based on a commercial whey protein hydrolysate. Consumption of HP diets and resistance training significantly affected food intake, body weight and body composition, as well as the plasma levels of total cholesterol, HDL-cholesterol and TAG. The buffering action of resistance training on such diet-induced alterations was especially evident in the levels of plasma TAG. Consumption of HP diets led to a considerable increase in kidney weight, urinary volume and acidity, as well as in the urinary excretion of Ca, with a parallel reduction in the urinary excretion of citrate (P < 0·05). No apparent deleterious effect on bone mineral content was found. In conclusion, consumption of HP diets caused alterations in renal health status and some metabolic parameters, but did not seem to affect bone status. Resistance training had a protective action against alterations of renal health status and some metabolic parameters such as plasma TAG.

Antioxidant and antiproliferative potential of ethanolic extracts from Moringa oleifera, Tropaeolum tuberosum and Annona cherimola in colorrectal cancer cells.

Moringa oleifera, Tropaeolum tuberosum and Annona cherimola are medicinal plants traditionally used in Ecuador. However, their therapeutic properties are not completely known. We analyzed chromatographically ethanolic extracts of the seeds of M. oleifera, A. cherimola and the tubers of T. tuberosum; all presented a high content of polyphenols. The extract of A. cherimola showed the highest antioxidant activity and M. oleifera had the highest capacity to enhance the activity of detoxifying enzymes such as glutathione S-transferase and quinone oxidoreductase. The antitumor effect of these extracts was evaluated in vitro with colorectal cancer (CRC) cell lines T84, HCT-15, SW480 and HT-29, as well as with cancer stem cells (CSCs). A. cherimola and M. oleifera extracts presented the lowest IC50 in T-84 and HCT-15 (resistant) cells, respectively, as well as the highest level of inhibition of proliferation in multicellular tumor spheroids of HCT-15 cells. The inhibitory effect on CSCs is noteworthy because in vivo, these cells are often responsible for cancer recurrences and resistance to chemotherapy. Moreover, all extracts showed a synergistic activity with 5-Fu. The antiproliferative mechanism of the extracts was related to overexpression of caspases 9, 8 and 3 and increased production of reactive oxygen species. In addition, we observed cell death by autophagy in M. oleifera and T. tuberosum extracts. Therefore, these ethanolic extracts are excellent candidates for future molecular analysis of the presence of bioactive compounds and in vivo studies which could improve colon cancer therapy.

Antitumor Effect of the Ethanolic Extract from Seeds of Euphorbia lathyris in Colorectal Cancer.

The seeds of Euphorbia lathyris have been used in traditional medicine to treat various medical conditions. However, neither all of their active biocompounds nor the molecular mechanisms underlying their therapeutic effects have been described. A new ethanolic extract of defatted flour from mature seeds of Euphorbia lathyris showed a high total polyphenol content and significant antioxidant activity. Chromatographic analysis showed that esculetin, euphorbetin, gaultherin, and kaempferol-3-rutinoside were the most abundant polyphenolic bioactive compounds. Antiproliferative assays showed a high and selective antitumor activity against colon cancer cell lines (T84 and HCT-15). In addition, a significant antiproliferative activity against glioblastoma multiforme cells was also demonstrated. Its mechanism of action to induce cell death was mediated by the overexpression of caspases 9, 3, and 8, and by activation of autophagy. Interestingly, a reduction in the migration capacity of colon cancer cells and a significant antiangiogenic effect on human umbilical vein endothelial cells were also demonstrated. Finally, the extract significantly reduced the subpopulations of cancer stem cells. This extract could be the basis to develop new therapeutic strategies for the treatment of colon cancer, although further experiments will be necessary to determine its in vivo effects.

Anemonia sulcata and Its Symbiont Symbiodinium as a Source of Anti-Tumor and Anti-Oxoxidant Compounds for Colon Cancer Therapy: A Preliminary in Vitro Study.

Recently, invertebrate marine species have been investigated for the presence of natural products with antitumor activity. We analyzed the invertebrate Anemonia sulcata with (W) and without (W/O) the presence of its microalgal symbiont Symbiodinium as a source of bioactive compounds that may be applied in the therapy and/or prevention of colorectal cancer (CRC). Animals were mechanically homogenized and subjected to ethanolic extraction. The proximate composition and fatty acid profile were determined. In addition, an in vitro digestion was performed to study the potentially dialyzable fraction. The antioxidant and antitumor activity of the samples and the digestion products were analyzed in CRC cells in vitro. Our results show a high concentration of polyunsaturated fatty acid in the anemone and a great antioxidant capacity, which demonstrated the ability to prevent cell death and a high antitumor activity of the crude homogenates against CRC cells and multicellular tumor spheroids, especially W/O symbiont. These preliminary results support that Anemonia sulcata could be a source of bioactive compounds with antioxidant and antitumor potential against CRC and that the absence of its symbiont may enhance these properties. Further studies will be necessary to define the bioactive compounds of Anemonia sulcata and their mechanisms of action.