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.
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.
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.
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.
Background/Objective: Colon cancer poses a significant health burden, with current treatments often associated with severe side effects and limited effectiveness for some patients. Natural products are gaining interest as adjuvant therapies, potentially reducing side effects and improving responses to conventional treatments. We previously highlighted the potent antineoplastic effects of organic extracts derived from the Lebanese red algae Jania rubens. This study, investigated the anticancer activities of polysaccharide, protein, and lipid extracts from J. rubens, which may serve as adjuvant therapies to enhance conventional treatments. Methods: we employed colorimetric assays, wound healing assays, and cell cycle analysis to evaluate the anticancer activities of the extracts. The polysaccharide extract was characterized for sulfate content and structure using barium chloride-gelatin and FT-IR methods. Results: All J. rubens extracts exhibited significant anticancer effects, with the polysaccharide extract showing particularly strong cytotoxicity, apoptosis induction, and antiproliferative and anti-migratory activities. Conclusion: These findings confirm that J. rubens is a source of bioactive compounds with anticancer potential. Further investigations are needed to elucidate the molecular pathways targeted by J. rubens extracts in cancer cells.
The red seaweed Jania rubens (J. rubens) is prevalent along the Lebanese coast and has drawn attention for its notable antineoplastic properties. Our previous data showed that its dichloromethane–methanol (DM) extract possesses antioxidant, cytotoxic, and anti-migratory effects on colon cancer cells. In the present study, a GC-MS analysis of DM extract identified a diverse profile of bioactive compounds, including flavonoids and pyrazole derivatives with antioxidant and anticancer activities. In vitro assays demonstrated that the DM extract exerts significant cytotoxic activity against various cancer cell lines, including colon, breast, and cervical types. Further investigation into the underlying molecular mechanisms revealed that the extract induces G2/M cell cycle arrest and reduces the expression of EMT (epithelial–mesenchymal transition) markers, N-cadherin and Twist. In addition, the extract showed anti-metastatic properties through its ability to decrease MMP-2 and MMP-9 activity. Mechanistically, DM caused a substantial reduction in Ten-Eleven Translocation (TET) enzymes TET-1, TET-2, and TET-3, which are essential DNA demethylation regulators, thus decreasing their enzymatic product 5-hydroxymethylcytosine (5-hmC). Interestingly, despite a significant increase in intracellular ROS (reactive oxygen species), suggesting a contribution to cytotoxicity, no substantial change in the biogenesis of promyelocytic leukemia nuclear bodies (PML-NBs) was detected. These findings demonstrate that J. rubens DM extract contains bioactive compounds with multiple anticancer effects, thus making it a promising candidate for developing new therapeutic agents.