Extrato rico em galactoglucomanana (GGM) inibe proliferação celular, atenua estresse oxidativo e lesões pré-neoplásicas em ratos induzidos à carcinogênese colorretal

Abstract

Galactoglucomannan (GGM) is the predominant hemicellulose in coniferous trees such as Norway spruce. The present study investigated the bioactive effects of an aqueous extract rich in GGM in experimental models. The GGM underwent the process of simulated in vitro gastrointestinal digestion and the fractions resulting from the oral, gastric and intestinal phases were subjected to chemical analysis to investigate the content of phenolic compounds, bioaccessibility and antioxidant activity. The extracts were tested on cancer cell lines to evaluate their antiproliferative, cytotoxic and antioxidant effects. The role of GGM in pre-neoplastic lesions in the colon and modulation of the intestinal microbiota was investigated in Wistar rats chemically induced colorectal cancer (CRC). The results of the chemical analysis showed that the gastrointestinal tract decreased the content of total phenolic compounds (from 33.12 to 19.06mg AGE/g), reducing its bioaccessibility to 57.54% in relation to the crude and, consequently, decreasing its capacity antioxidant (FRAP = from 96.12 to 10.52mg of AAE/g; DPPH = from 77.01 to 10.30mg of AAE/g). However, cellular analysis did not support this finding and confirmed the antioxidant action of GGM. The results of IC50 (between 21.34 and >200μg AGE/mL), IG50 (between 1.97 and 126.4μg AGE/mL) and LC50 (between 24.72 and > 200μg AGE/mL) indicated an antiproliferative behavior, cytotoxic and lethal effect of GGM in the tested cancer cell lines. GGM attenuated the initiation and progression of colon cancer, reducing the foci of aberrant crypts in animals and was able to modify the intestinal microbiota by disrupting the balance between the Firmicutes/Bacteroidetes phyla. With this evidence, it is possible to suggest that GGM provides chemopreventive protection against the development of colon cancer and operates as an intracellular antioxidant agent.