Extended chain conformation of β-glucan and its effect on antitumor activity

Abstract

Mushrooms are known as a delicacy due to their delicious taste and rich nutrition, and their β-glucans have antitumor activity. Here, a triple helical β-glucan (THG) isolated from Lentinus edodes was successfully fractionated into nine fractions with different weight-average molecular weights (M_w) through ultrasonic irradiation. The M_w, radius of gyration (〈R_g〉_z), hydrodynamic radius (〈R_h〉_z), structure-sensitive parameters (ρ), contour length (L), persistence length (q) and molar mass per contour length (M_L) were characterized by static light scattering (SLS), dynamic light scattering (DLS), and atomic force microscopy (AFM). The results indicated that THG displayed an extended chain conformation with ρ values of 2.1 ± 0.1 for the nine fractions, as well as M_L and q values of 2160 nm⁻¹ and 110 nm in water, which were consistent with the data for triple helical polysaccharides. In combination with the apparent length (L_ap) values visualized with AFM and M_w, the molar mass per apparent contour length (M_Lap) was calculated to be 2242 nm⁻¹, which was similar to that obtained from SLS according to the wormlike cylinder model. Thus, we established a novel method using AFM for characterizing the chain stiffness of polysaccharides. The results from an animal assay demonstrated that THG significantly inhibited H22 tumor growth without damage to organisms, and the THG fractions with relatively low molecular weight and/or higher stiffness showed stronger antitumor activity, revealing the significant molecular weight- and chain conformation-dependences of antitumor activity. Moreover, a schematic model to describe the interaction between THG and receptors on the immune cell membrane was proposed to illustrate these results. This work provides important information for characterizing the chain conformation of polysaccharides and understanding the relationship between structure and antitumor activity, which is relevant for the treatment of hepatocellular carcinoma in clinic.