1. Leukemia cells apoptosis by a newly discovered heterogeneous polysaccharide from Angelica sinensis (Oliv.) Diels.
- Author
-
Liu, Wenjuan, Xiao, Kaimin, Ren, Li, Sui, Yi, Chen, Jie, Zhang, Tian, Li, Xiao-Qiang, and Cao, Wei
- Subjects
- *
POLYSACCHARIDES , *DONG quai , *APOPTOSIS , *LEUKEMIA , *ACUTE myeloid leukemia , *GALACTURONIC acid , *GALACTOSIDASES - Abstract
• An anti-leukemia polysaccharide (APS-2I) was isolated from Chinese Angelica root. • The APS-2I digested fraction (G-4) exhibits higher anti-leukemia effect than APS-2I in vitro and vivo. • APS-2I and G-4 bind to Gal-3 with Kd of 9.35 ± 0.3 μM and 1.97 ± 0.7 μM respectively. • Backbone of APS-2I contains 1,4-Gal p A, 1,4-Gal p 6Me,1,3-Rha p , 1,2,6-Man p, 1,6-Gal p and 1,2-Man p. • Branches of APS-2I contains T-Ara f, 1,4-Gal p , 1,3-Ara f , 1,5-Ara f and 1,3,5-Ara f , 1,6-Gal p. Galectin-3 (Gal-3) is a potential target for acute myeloid leukemia therapeutics which contains a carbohydrate-recognition domain. However, the development of polysaccharide inhibitors against Gal-3 is insufficient. In this research, we found a polysaccharide from Angelica sinensis (Oliv.) Diels, named APS-2I, that can bind to Gal-3 with dissociation constant (Kd) of 9.35 ± 0.3 μM and activate the intrinsic apoptosis pathways to induce leukemia cells apoptosis. APS-2I is a homogeneous polysaccharide with a molecular weight of 7.2 × 105 Da, that composes of mannose, rhamnose, galacturonic acid, glucose, galactose and arabinose with a ratio of 4:5:1:10:23:39. In addition, a galactosidase digested fraction of APS-2I named G-4 showed higher affinity to Gal-3 with the Kd of 1.97 ± 0.7 μM and higher apoptosis inducing effect on leukemia cells, which demonstrated that G-4 contains the bio-active structural region of APS-2I. This study provides effective basis for structural analysis and the anti-leukemia mechanism of Angelica polysaccharide APS-2I. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF