Leukemia cells apoptosis by a newly discovered heterogeneous polysaccharide from Angelica sinensis (Oliv.) Diels
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Published on: June 16, 2019
Wenjuan Liu1, Kaimin Xiao2, Li Ren2
1Shaanxi Key Laboratory of Natural Products & Chemical Biology, School of Chemistry & Pharmacy, Northwest A&F University, Yangling, 712100, China; Department of Pharmacology and Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, China; Department of Natural Medicine & Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, China.
Abstract:
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.
