ABSTRACT
Underutilized marine food products such as cephalopods' ink could be sources of bioactive compounds providing health benefits. This study aimed to assess the anti-proliferative and anti-inflammatory effects from Octopus vulgaris ink extracts (hexane-, ethyl acetate-, dichloromethane- (DM), and water extracts) using human colorectal (HT-29/HCT116) and breast (MDA-MB-231) cancer cells, and LPS-challenged murine RAW 264.7 cells. Except by ethyl-acetate, all of the extracts exhibited anti-proliferative effects without being cytotoxic to ARPE-19 and RAW 264.7 cells. Among DM fractions (F1/F2/F3), DM-F2 showed the highest anti-proliferative effect (LC50 = 52.64 µg/mL), inducing pro-apoptotic morphological disruptions in HCT116 cells. On RAW 264.7 cells, DM-F2 displayed the lowest nitrites reduction and up-regulation of key-cytokines from the JAK-STAT, PI3K-Akt, and IL-17 pathways. Compared to control, DM-F2 increased IL-4 and decreased NF-κB fluorometric expression in peripheral blood mononuclear cells (PBMCs). Metabolomic analysis of DM-F2 highlighted hexadecanoic acid and 1-(15-methyl-1-oxohexadecyl)-pyrrolidine as the most important metabolites. These compounds also exhibited high in silico binding affinity (-4.6 to -5.8 kcal/mol) to IL-1α, IL-1ß, and IL-2. Results suggested the joint immuno-modulatory and anti-proliferative effect derived from selected compounds of underutilized marine food products such as ink. This is the first report of such biological activities in extracts from O. vulgaris ink.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Cell Proliferation/drug effects , Octopodiformes/chemistry , Animals , Cytokines/metabolism , HCT116 Cells , Humans , Inflammation Mediators/metabolism , Macrophages/drug effects , Macrophages/metabolism , Metabolomics , Methylene Chloride/chemistry , Mice , Nitrites/metabolism , RAW 264.7 Cells , Signal TransductionABSTRACT
BACKGROUND: Cancer is a disease characterized by the invasion and uncontrolled growth of cells. One of the best ways to minimize the harmful effects of mutagens is through the use of natural antimutagens. In this regard, the search for new antimutagens that act in the chemoprevention could represent a promising field in this area. OBJECTIVE: In this study biological potential of 11 fractions from Coccoloba uvifera L. leaf hexane extract was evaluated by several in vitro tests. METHODS: Leaves were lyophilized and hexane extraction was performed. The extract was fractionated by column chromatography with hexane, ethyl acetate, and methanol. The antimutagenic (Ames test), antiproliferative (MTT test), and antioxidant capacity (DPPH, ABTS, and ferrous ion chelation) of the fractions were evaluated. RESULTS: Fractions 4, 6, 8, and 9 have antimutagenic activity (against sodium azide in strain TA100), fraction 11 showed antiproliferative capacity (IC50 of 24 ± 9 µg/mL in cells of HCT 116). The fractions with the highest activity were analyzed by HPLC-MS and lupeol, acacetin, and ß-sitosterol were identified. CONCLUSION: This study demonstrates, for the first time, the bioactivity of C. uvifera leaf as a new source of High Biological Value Compounds (HBVC), which can be of interest to the food and pharmaceutical industries.
