Angelica polysaccharides inhibit the growth and promote the apoptosis of U251 glioma cells in vitro and in vivo

Abstract

Background: Angelica sinensis (Oliv) Diels (Apiaceae) is a traditional medicine that has been used for more than 2000 years in China. It exhibits various therapeutic effects including neuroprotective, anti-oxidant, anti-inflammatory, and immunomodulatory activities. Angelica polysaccharides (APs), bioactive constituents of Angelica have been shown to be responsible for these effects; however, the utility of APs for the treatment of glioma and their mechanism of action remain to be elucidated.

Purpose: In this study, we investigated the inhibitory effects of APs on a glioma cell line and their molecular mechanism of action.

Study design: U251 cells were utilized to confirm the effects of APs on glioma.

Methods: The human glioblastoma cell line U251 was utilized for both in vitro and in vivo models, in which we tested the effects of APs. Flow cytometry, gene expression analysis, western blotting, and MTT assays were used to elucidate the effects of APs on cell proliferation, cell cycle, and apoptosis.

Results: The results demonstrated that APs significantly inhibited the growth and proliferation of U251 cells and induced their apoptosis. Furthermore, APs effectively reduced the expression of several cell cycle regulators: cyclins D1, B, and E. The apoptosis suppressor protein Bcl-2 was also downregulated, and the expression of pro-apoptotic proteins Bax and cleaved-caspase-3 increased. Additionally, APs inhibited the transforming growth factor (TGF)-β signaling pathway and stimulated the expression of E-cadherin, thus prohibiting cell growth.

Conclusion: In conclusion, the results indicate that APs attenuate the tumorigenicity of glioma cells and promote their apoptosis by suppressing the TGF-β signaling pathway. The present study therefore provides evidence of the inhibitory effects of APs against glioma progression, and proposes their potential application as alternative therapeutic agents for glioma.

Keywords: AS, angelica sinensis (oliv.) diels; Abbreviations: MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Angelica polysaccharides; Apoptosis; Aps, angelica polysaccharides; Cell cycle; Cell proliferation; Cis, cisplatin; EMT, esenchymal transition; Glioma; PBS, phosphate-buffered saline; TGF, transforming growth factor; TUNEL, terminal deoxynucleotidyl transferase dUTP nick-end labeling.