Vitamin C enhances co-localization of novel TET1 nuclear bodies with both Cajal and PML bodies in colorectal cancer cells.

Deregulation of ten-eleven Translocation protein 1 (TET1) is commonly reported to induce imbalances in gene expression and subsequently to colorectal cancer development (CRC). On the other hand, vitamin C (VitC) improves the prognosis of colorectal cancer by reprogramming the cancer epigenome and limiting chemotherapeutic drug resistance events. In this study, we aimed to characterize TET1-specific subcellular compartments and evaluate the effect of VitC on TET1 compartmentalization in colonic tumour cells. We demonstrated that TET1 is concentrated in coarse nuclear bodies (NB) and 5-hydroxymethylcytosine (5hmC) in foci in colorectal cancer cells (HCT116, Caco-2, and HT-29). To our knowledge, this is the first report of a novel intracellular localization profile of TET1 and its demethylation marker, 5hmC, in CRC cells. Interestingly, we found that TET1-NBs frequently interacted with Cajal bodies, but not with promyelocytic leukaemia (PML) bodies. In addition, we report that VitC treatment of HCT116 cells induces 5hmC foci biogenesis and triggers 5hmC marks to form active complexes with nuclear body components, including both Cajal and PML proteins. Our data highlight novel NB-concentrating TET1 in CRC cells and demonstrate that VitC modulates TET1-NBs' interactions with other nuclear structures. These findings reveal novel TET1-dependent cellular functions and potentially provide new insights for CRC management.

The Lebanese Red Algae Jania rubens: Promising Biomolecules against Colon Cancer Cells.

Colorectal cancer (CRC) is ranked the second most lethal type of tumor globally. Thus, developing novel anti-cancer therapeutics that are less aggressive and more potent is needed. Recently, natural bioactive molecules are gaining interest as complementary and supportive antineoplastic treatments due to their safety, effectiveness, and low cost. Jania rubens (J. rubens) is a red coral seaweed abundant in the Mediterranean and bears a significant pharmacological essence. Despite its therapeutic potential, the natural biomolecules extracted from this alga are poorly identified. In this study, the proximal analysis revealed high levels of total ash content (66%), 11.3% proteins, 14.5% carbohydrates, and only 4.5% lipids. The elemental identification showed magnesium and calcium were high among its macro minerals, (24 ± 0.5 mg/g) and (33 ± 0.5 mg/g), respectively. The Chlorophyll of J. rubens was dominated by other pigments with (0.82 ± 0.02 mg/g). A 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay identified effective antioxidant activity in various J. rubens extracts. More importantly, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tetrazolium reduction and wound healing assays indicate that organic extracts from J. rubens significantly counteract the proliferation of colon cancer cell lines (HCT-116 and HT-29) and inhibit their migratory and metastatic properties in a dose and time-dependent manner. Overall, this study provides insight into the physicochemical properties of red seaweed, J. rubens, and identifies its significant antioxidant, cytotoxic, and anti-migratory potential on two colorectal cell lines, HCT-116 and HT-29.

Fucoidan and Alginate from the Brown Algae Colpomenia sinuosa and Their Combination with Vitamin C Trigger Apoptosis in Colon Cancer.

Brown seaweeds are producers of bioactive molecules which are known to inhibit oncogenic growth. Here, we investigated the antioxidant, cytotoxic, and apoptotic effects of two polysaccharides from the brown algae Colpomenia sinuosa, namely fucoidan and alginate, in a panel of cancer cell lines and evaluated their effects when combined with vitamin C. Fucoidan and alginate were isolated from brown algae and characterized by HPLC, FTIR, and NMR spectroscopy. The results indicated that highly sulfated fucoidans had higher antioxidant and cytotoxic effects than alginate. Human colon cancer cells were the most sensitive to the algal treatments, with fucoidan having an IC50 value (618.9 µg/mL-1) lower than that of alginate (690 µg/mL-1). The production of reactive oxygen species was increased upon treatment of HCT-116 cells with fucoidan and alginate, which suggest that these compounds may trigger cell death via oxidative damage. The combination of fucoidan with vitamin C showed enhanced effects compared to treatment with fucoidan alone, as evidenced by the significant inhibitory effects on HCT-116 colon cancer cell viability. The combination of the algal polysaccharides with vitamin C caused enhanced degeneration in the nuclei of cells, as evidenced by DAPI staining and increased the subG1 population, suggesting the induction of cell death. Together, these results suggest that fucoidan and alginate from the brown algae C. sinuosa are promising anticancer compounds, particularly when used in combination with vitamin C.

The Cytotoxic Effect of Apis mellifera Venom with a Synergistic Potential of Its Two Main Components-Melittin and PLA2-On Colon Cancer HCT116 Cell Lines.

Colon carcinogenesis is ranked second globally among human diseases after cardiovascular failures. Bee venom (BV) has been shown to possess in vitro anticancer effects against several types of cancer cells. The two main biopeptides of Apis mellifera BV, namely, melittin (MEL) and phospholipase A2 (PLA2), are suspected to be the biomolecules responsible for the anticancer activity. The present work aims to evaluate the cytotoxic effect of the A. mellifera venom on human colon carcinoma cells (HCT116), and to assess the synergistic effect of MEL and PLA2 on these cells. After analyzing, through high-pressure liquid chromatography, the proportions of MEL and PLA2 on BV, we have established a cell viability assay to evaluate the effect of BV, MEL, PLA2, and a mixture of MEL and PLA2 on the HCT116 cells. Results obtained showed a strong cytotoxicity effect induced by the A. mellifera venom and to a lower extent MEL or PLA2 alone. Remarkably, when MEL and PLA2 were added together, their cytotoxic effect was greatly improved, suggesting a synergistic activity on HCT116 cells. These findings confirm the cytotoxic effect of the A. mellifera venom and highlight the presence of synergistic potential activities between MEL and PLA2, possibly inducing membrane disruption of HCT116 cancer cells. Altogether, these results could serve as a basis for the development of new anticancer treatments.

The Cytotoxic and Apoptotic Effects of the Brown Algae Colpomenia sinuosa are Mediated by the Generation of Reactive Oxygen Species.

Brown algae are a novel resource of biogenic molecules, however few studies have been conducted in the Mediterranean to assess the cytotoxic mechanisms of algal-derived compounds. This study focuses on the antineoplastic activity of extracts from non-investigated algae of the Lebanese coast, Colpomenia sinuosa. Extracts' antineoplastic activities were evaluated by MTT and trypan blue on different tumorigenic cells. Results indicated that the most potent extract was obtained by soxhlet using dichloromethane:methanol solvent (DM soxhlet) against HCT-116. Wound healing assay confirmed that this extract decreased the migration potential of HCT-116 cells with minimal effects on non-tumorigenic cells. It also induced an increase in the subG1 population as determined by flow cytometry. Western blot analysis demonstrated that apoptosis in treated HCT-116 cells was induced via upregulation of p21 protein and downregulation of the anti-apoptotic Bcl 2, which led to caspases activation. The latter, catalyzes the degradation of PARP-1, and thus suppresses cancer proliferation. Morphological alterations, further confirmed apoptosis. A strong pro-oxidant activity evidenced by the enhanced generation of reactive oxygen species (ROS) was observed in HCT-116 treated cells. Interestingly, a strong antioxidant effectively blocked effect induced by the extract. These results indicate that C. sinuosa is a source of bioactive compounds possessing pro-apoptotic and anti-migratory efficacy.

Effect of Processed Chickpea Flour Incorporation on Sensory Properties of Mankoushe Zaatar.

Chickpea flour is known to have good nutritional values. Nevertheless, it is commonly made from ground grains, and characterized by an "off-flavor". Processing of chickpea grains before flour formation reduces the intensity of the off-flavor. Therefore, two experiments were conducted: first to examine the effect of conventional processing (soaking, boiling, and drying) on the nutritional composition of the chickpea flour; and second, to investigate the impact of processed chickpea flour incorporation with different ratios on the sensory properties of mankoushe zaatar, a popular Lebanese pastry, usually made up of refined wheat flour. Chickpea flour was found to be nutritionally superior compared to refined wheat flour, and conventional processing of the flour was found not to affect its content of protein, fats, carbohydrates, and phosphorus, while total dietary and crude fibers were significantly increased. The fatty acid profile was minimally affected, while magnesium and potassium were reduced. The sensory test conducted among panelists (n = 60) showed that the incorporation of processed chickpea flour into the dough of mankoushe zaatar with ratios of 30% and 50% provided an end-product with better taste and overall acceptability compared to the regular mankoushe. Hence, conventionally processed chickpea flour can be used as a fortifier to improve the nutritional quality of bakery products without negatively affecting their sensory properties.

Impact of Pre-Processed Chickpea Flour Incorporation into "Mankoushe" on Appetite Hormones and Scores.

Recently, there has been an increasing interest in integrating pulse flours into pastries and baked products to improve their nutritional and health benefits. "Mankoushe," a popular Lebanese pastry made up of refined wheat flour was enriched with chickpea flour that is of better nutritional value, and its postprandial glycemia, insulinemia, lipidemia and appetite measures were monitored. A randomized cross-over study was performed on sixteen healthy Lebanese females, age (years): 22.90 ± 3.00, and BMI (kg/m²): 22.70 ± 2.65. Over-night fasted females were asked to consume two iso-energetic meals (201 g; 681 kcal) on two separate days, three days apart. One meal was the "Regular Mankoushe" (RM) made with white flour 100%, and the second meal was the "Chickpeas Mankoushe" (CM) made with a mixture of wheat/chickpea flour (70/30). Blood samples were collected 15 min before meal ingest and at 30, 90, 150 and 210 min postprandial. Glucose, insulin, triglycerides (TG), ghrelin, and glucagon-like peptide 1 (GLP-1) plasma levels were measured. Subjective appetite rating and food intake were also assessed. Incorporation of pre-processed chickpea flour into "Mankoushe" as 30% of the dough was associated with a modest reduction in both glucose and insulin levels, and TG was minimally affected. At the level of appetite hormones, changes in GLP-1 were similar, whereas the reduction in ghrelin was significantly lower after the RM meal and thus favored a higher satiating effect compared to CM. This was not paralleled by a similar change in subjective appetite scores and subsequent energy intake. In conclusion, findings suggest that pre-processed chickpea flour could be a promising functional ingredient of traditional pastries to improve their nutritional quality. Nevertheless, further investigations are warranted regarding its satiating effect.