Effects of the Molecular Weight and the Degree of Deacetylation of Chitosan Oligosaccharides on Antitumor Activity

Jae Kweon Park,Ha Na Choi,Mi Ja Chung,Yong Il Park

doi:10.3390/ijms12010266

Jae Kweon Park, Ha Na Choi + Show 2 more

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https://doi.org/10.3390/ijms12010266

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Abstract

Effects of the degree of deacetylation (DDA) and the molecular mass of chitosan oligosaccharides (CTS-OS), obtained from the enzymatic hydrolysis of high molecular weight chitosan (HMWC), on antitumor activity was explored. The DDA and molecular weights of CTS-OS were determined by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-TOF MS) analysis. The CTS-OS were found to be a mixture of mainly dimers (18.8%), trimers (24.8%), tetramers (24.9%), pentamers (17.7%), hexamers (7.1%), heptamers (3.3%), and octamers (3.4%). The CTS-OS were further fractionated by gel-filtration chromatography into two major fractions: (1) COS, consisting of glucosamine (GlcN)n, n = 3–5 with DDA 100%; and (2) HOS, consisting of (GlcN)5 as the minimum residues and varying number of N-acetylglucosamine (GlcNAc)n, n = 1–2 with DDA about 87.5% in random order. The cytotoxicities, expressed as the concentration needed for 50% cell death (CC50), of CTS-OS, COS, and HOS against PC3 (prostate cancer cell), A549 (lung cancer cell), and HepG2 (hepatoma cell), were determined to be 25 μg·mL−1, 25 μg·mL−1, and 50 μg·mL−1, respectively. The HMWC was approximately 50% less effective than both CTS-OS and COS. These results demonstrate that the molecular weight and DDA of chitosan oligosaccharides are important factors for suppressing cancer cell growth.

Highlights

IntroductionChitosan is a linear heteropolysaccharide composed of -(1,4)-linked-D-glucosamine (GlcN) and N-acetylglucosamine (GlcNAc), which is derived from chitin
Chitin is the second most abundant naturally occurred homopolysaccharide composed of-(1,4)-linked-D-N-acetylglucosamine (GlcNAc) after cellulose
The chitosan-oligosaccharides (CTS-OS) in the supernatant after hydrolysis of high molecular weight chitosan (HMWC) with a chitosanase were recovered and lyophilized by the method described in the Materials and Methods to seek the feasibility of CTS-OS for the test of antitumor efficacy

Summary

Introduction

Chitosan is a linear heteropolysaccharide composed of -(1,4)-linked-D-glucosamine (GlcN) and N-acetylglucosamine (GlcNAc), which is derived from chitin. The study on chitosan has attracted interest in converting it into more soluble form of chitosan-oligosaccharides, hereafter referred to CTS-OS, which exhibit remarkable biological activities [1,2,3,4,5]; they are non-toxic, biocompatible and biodegradable [6], including antibacterial antifungal, antitumor and stimulating immunoenhancing properties. It is implicated that the biological activities of CTS-OS significantly depend on their molecular weight and the degree of deacetylation (DDA) of the parental material chitosan. This is affected by the distribution pattern of GlcN/GlcNAc along the oligomeric chain of CTS-OS [7,8,9]. In order to study the relationship between structure and biological activity, structurally well-defined

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