Aglycone Ebselen and beta-D-Xyloside Primed Glycosaminoglycans Co-contribute to Ebselen beta-D-Xyloside-Induced Cytotoxicity

作者：Tang, Yang; Zhang, Siqi; Chang, Yajing; Fan, Dacheng; De Agostini, Ariane; Zhang, Lijuan^*; Jiang, Tao^*

来源：Journal of Medicinal Chemistry, 2018, 61(7): 2937-2948.

DOI：10.1021/acs.jmedchem.7b01835

• COLON-CANCER CELLS
• ACTIVE ORGANOSELENIUM COMPOUND
• HEPARAN-SULFATE
• GLUTATHIONE-PEROXIDASE
• IN-VITRO
• 5-HYDROXY POLYMETHOXYFLAVONES
• TUMOR ATTENUATION
• SIGNALING COMPLEX
• BIOSYNTHESIS
• GROWTH

Most beta-D-xylosides with hydrophobic aglycones are nontoxic primers for glycosaminoglycan assembly in animal cells. However, when Ebselen was conjugated to D-xylose, D-glucose, D-galactose, and D-lactose (8A-D), only Ebselen beta-D-xyloside (8A) showed significant cytotoxicity in human cancer cells. The following facts indicated that the aglycone Ebselen and beta-D-xyloside primed glycosaminoglycans co-contributed to the observed cytotoxicity: 1. Ebselen induced S phase cell cycle arrest, whereas 8A induced G2/M cell cycle arrest; 2. 8A augmented early and late phase cancer cell apoptosis significantly compared to that of Ebselen and 8B-D; 3. Both 8A and phenyl-beta-D-xyloside primed glycosaminoglycans with similar disaccharide compositions in CHO-pgsA745 cells; 4. Glycosaminoglycans could be detected inside of cells only when treated with 8A, indicating Ebselen contributed to the unique property of intracellular localization of the primed glycosaminoglycans. Thus, 8A represents a lead compound for the development of novel antitumor strategy by targeting glycosaminoglycans.

• 出版日期2018-4-12
• 单位中国海洋大学; 青岛大学