Anti-tumor effect of β-glucan from Lentinus edodes and the underlying mechanism.

Hui Xu,Xiaojuan Xu,Siwei Zou,Lina Zhang

doi:10.1038/srep28802

Abstract

β-Glucans are well known for its various bioactivities, but the underlying mechanism has not been fully understood. This study focuses on the anti-tumor effect and the potential mechanism of a branched β-(1, 3)-glucan (LNT) extracted from Lentinus edodes. The in vivo data indicated that LNT showed a profound inhibition ratio of ~75% against S-180 tumor growth, even significantly higher than the positive control of Cytoxan (~54%). Interestingly, LNT sharply promoted immune cells accumulation into tumors accompanied by cell apoptosis and inhibition of cell proliferation during tumor development. Furthermore, LNT not only up-regulated expressions of the tumor suppressor p53, cell cycle arrestin p21 and pro-apoptotic proteins of Bax and caspase 3/9, but also down-regulated PARP1 and anti-apoptotic protein Bcl-2 expressions in tumor tissues. It was first found that LNT initiated p53-dependent signaling pathway to suppress cell proliferation in vitro, and the caspase-dependent pathway to induce cell apoptosis in vivo. The underlying anti-tumor mechanism was proposed that LNT activated immune responses to induce cell apoptosis through caspase 3-dependent signaling pathway and to inhibit cell proliferation possibly via p53-dependent signaling pathway in vivo. Besides, LNT inhibited angiogenesis by suppressing VEGF expression, leading to slow progression of tumors.

Highlights

Cancer is a universal health problem with high morbidity and mortality, constituting an enormous burden on society in more and less economically developed countries alike
Lentinan (LNT), a β-1, 3-glucan with two β-1, 6-glucose branches every five glucose residues in the backbone from Lentinus edodes[9], as the first medicinal macrofungus to enter the realm of modern biotechnology[10], is especially striking for its anti-tumor activity possibly due to its unique triple helical conformation[11]
We have demonstrated that LNT can stimulate macrophage-like RAW264.7 cells through activation of mitogen-activated protein kinases (MAPKs) and nuclear transcription factor NF-κB p6512

Summary

Introduction

Cancer is a universal health problem with high morbidity and mortality, constituting an enormous burden on society in more and less economically developed countries alike. Unlike existing small molecular anti-cancer chemicals, polysaccharides are well known to have no toxic side effects. Several polysaccharides such as PSK and schizophyllan are currently used clinically as anti-tumor agents[5,6] mainly in Japan, but have not been used worldwide. In this study, we performed in vivo (mice sarcoma S-180 tumor model) and in vitro (S-180 and human cervical carcinoma Hela cells) experiments to explore the potential mechanism of anti-tumor by using confocal microscopy, western blot, histology and immunohistochemical staining, and immunofluorescence staining etc. The in vivo data demonstrated that LNT showed remarkable anti-tumor effect through activating immune cells to promote tumor cell apoptosis via caspase-dependent signaling pathway, and to inhibit tumor cell proliferation possibly via p53-dependent pathway. Our results will provide a better understanding of anti-tumor action for β-glucans

Methods

Results

Conclusion