Preparation, antiangiogenic and antitumoral activities of the chemically sulfated glucan from Phellinus ribis.
Two sulfated derivatives (PRP-S1 and PRP-S2) of a β-glucan from Phellinus ribis with different degrees of substitution were obtained by chlorosulfonic acid method. The derivatives could block formation of new vessels in zebrafish and inhibit the proliferation of human umbilical vein endothelial cells (HUVECs). The two sulfated derivatives had remarkably high antitumor activities in vivo (in BALB/c mice inoculated with H22 hepatocellular carcinoma) as well as in vitro (against human ovary cancer SKOV-3 cells), without producing any overt signs of general toxicity. The results of immunohistochemistry assay indicated that the derivatives significantly reduced the average number of microvessel density (MVD) and inhibited the expression of vascular endothelial growth factor (VEGF) in tumor. Thus, these derivatives exhibit pronounced antiangiogenic and antitumoral properties. Except for cytotoxic effects on tumor cells, it is reasonable to expect that the antitumoral effects of PRP-S1 and PRP-S2 are mediated via their antiangiogenic properties.
Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; National Glycoengineering Research Center, Shandong University, Jinan 250012, China.
Yuhong
Y
Liu
Department of Pharmacy, Shandong Tumor Hospital, Jinan 250117, China.
Yuguo
Y
Liu
School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
Haiqiang
H
Jiang
School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
Lingchuan
L
Xu
Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
Yanna
Y
Cheng
National Glycoengineering Research Center, Shandong University, Jinan 250012, China.
Peng George
PG
Wang
Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; National Glycoengineering Research Center, Shandong University, Jinan 250012, China. Electronic address: fswang@sdu.edu.cn.
Fengshan
F
Wang
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001487:Basidiomycota / Q000254:growth & development / Q000378:metabolism*; D002240:Carbohydrate Sequence; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005936:Glucans / Q000737:chemistry / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism; D047071:beta-Glucans / Q000737:chemistry*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D005936:Glucans; C000602520:PRP-S1 polysaccharide; C000602521:PRP-S2 polysaccharide; D047071:beta-Glucans; C078962:glucan sulfate
Antiangiogenesis; Antitumoral activity; Phellinus ribis; Sulfated derivatives; β-Glucan