Chitooligosaccharides antagonize the cytotoxic effect of glucosamine

Abstract

Chitooligosaccharides (COS) are partially hydrolyzed compounds derived from chitosan that exhibit a number of biological activities, including antitumor, antibacterial and antifungal properties. In this work, we examined the cytotoxicity of pure COS and oligomers A, B and C (solutions composed of different amounts of COS) produced by enzymatic hydrolysis using a crude enzyme extract produced by the fungus Metarhrizium anisopliae. The antiproliferative effect of these molecules was analyzed using tumor cell lines (HepG2 and HeLa cells) and in a normal cell line (3T3). The antioxidant activity was analyzed in several in vitro experiments. Glucosamine showed higher toxicity (approximately 92%) to all cell lines studied. However, the oligomers obtained after hydrolysis demonstrated no toxic effects on the normal cells (3T3). Furthermore, we showed that a small amount of other COS can decrease the cytotoxic effect of glucosamine against 3T3 cells, indicating that glucosamine could be used as an antitumor drug in the presence of other COS. In addition, different effects were found in antiproliferative assays, which depended on the COS composition in the oligomers (A, B and C), showing that a combination of them may be essential for developing antineoplastic drugs. Superoxide anion scavenging was the main antioxidant activity demonstrated by the COS and oligomers. This activity was also dependent on the oligomer composition of the chitosan hydrolysates. Further work will identify the ideal proportions of COS and glucosamine for maximizing the effects of these biological activities.

Cytotoxicity of Chitosan Oligomers Produced by Crude Enzyme Extract from the Fungus Metarhizium Anisopliae in Hepg2 and Hela Cells

“…The HepG2 cells, when treated with the chitooligosaccharides at a concentration of 0.2 mg/mL, induced cell viability of around 20% and at higher concentrations, it remained practically unaltered. These results corroborate literature data, in that chitooligosaccharides did not show any activity against Hep3B cells [14,15].…”

“…Similar results were found by Jeon and Kim [16], where chitooligosaccharides inhibited uterine tumors in rats by 73.6%. The modified chitooligosaccharides used in HeLa cells showed an IC 50 value of 0.45 mg/mL [14] and similar results were found in this study, where IC50 was 0.67 mg/mL. Kim and Rajapakse [12] observed that a mixture of chitosan oligomers from tetramer to pentamer could inhibit tumor cell growth in rats.…”

Marine Microbiological Enzymes: Studies with Multiple Strategies and Prospects

“…The degradation of chitin into oligosaccharides has promise that may be useful in numerous biological functions, such as antimicrobial activity and antitumor activity [135]. At present, chitooligosaccharides are mainly produced through chemical reactions in industry.…”

Knockdown of STAT3 expression in SKOV3 cells by biodegradable siRNA–PLGA/CSO conjugate micelles

“…A large number of researchers combine PEI with siRNA to form various siRNA-polymers because of the high-density positive charge of PEI [7,8], however, PEI has high toxicity [28]. On the other hand, CSO is biodegradable and has low toxicity [29]. It has also been reported that CSO has the function like antibiotic, antivirus, antitumor, decreasing blood lipids, hypoglycemic and anti-aging activities [30].…”