Polysaccharide-containing fraction from Artemisia argyi inhibits tumor cell-induced platelet aggregation by blocking interaction of podoplanin with C-type lectin-like receptor 2

• Published in: Yàowu shi͡p︡in fenxi Vol. 28; no. 1; pp. 115 - 123
• Main Authors: Tseng, Ching-Ping, Huang, Yu-Ling, Chang, Yao-Wen, Liao, Hsiang-Ruei, Chen, Yu-Li, Hsieh, Pei-Wen
• Format: Journal Article
• Language: English
• Published: China (Republic : 1949- ) Elsevier Taiwan LLC 01.01.2020; Food and Drug Administration
• Subjects: Acids; Agglomeration; Antagonists; Artemisia - classification; Artemisia argyi; Biocompatibility; Biological activity; Blood platelets; C-type lectin-like receptor 2; Cancer; Cell Line, Tumor; Chinese medicine; Collagen; Cytotoxicity; Dehydrogenases; Fractionation; Genomes; Glucose; Hematology; Herbal medicine; Humans; Lectins, C-Type - antagonists & inhibitors; Membrane Glycoproteins - antagonists & inhibitors; Metastases; Metastasis; Pharmacology; Phytochemicals - pharmacology; Plant Leaves - chemistry; Platelet aggregation; Platelet Aggregation - drug effects; Platelets; Podoplanin; Polysaccharides; Polysaccharides - pharmacology; Traditional Chinese medicine; Tumor cell-induced platelet aggregation; Tumor cells; Tumors; China; Taiwan; Tumor cell-induced platelet aggregation; DVT; CLEC-2; Co-HP; C-type lectin-like receptor 2; LDH; Polysaccharides; PMP; TCIPA; PDPN; Artemisia argyi; ALI; ARDS; Podoplanin; 2CP; TCM
• ISSN: 1021-9498; 2224-6614
• DOI: 10.1016/j.jfda.2019.08.002

Tumor cell-induced platelet aggregation (TCIPA) is a mechanism that involves the protection of tumor cells in the circulation and the promotion of tumor cell invasion and metastases. The C-type lectin-like receptor 2 (CLEC-2) that binds podoplanin (PDPN) is on the platelet surface and facilitates the TCIPA. Selective blockage of the PDPN-mediated platelet-tumor cell interaction is thereby a plausible strategy for inhibiting metastases. In a search for antagonists of PDPN- and tumor cell-induced platelet aggregation, traditional Chinese medicines were screened and it was found that the water extract of Artemisia argyi leaves selectively inhibited the PDPN-induced platelet aggregation. Bioactivity-guided fractionation analysis was performed for defining a polysaccharide-containing fraction (AAWAP) characterized by inhibition of PDPN activity and tumor cell-induced platelet aggregation. The pharmacological effects of AAWAP on PDPN-activated CLEC-2 signaling were determined by using Western blot and alpha screening analyses. AAWAP was non-toxic to the cells and platelets and it suppressed PDPN- and tumor cell-induced platelet aggregation by irreversibly blocking the interaction between PDPN and CLEC-2 in a dose-dependent manner. These findings indicate that AAWAP is an antagonist of the PDPN-CLEC-2 interaction. This action by AAWAP may result in the prevention of tumor cell metastases, and if so, could become an effective pharmacological agent in treating cancer patients. [Display omitted] •Bioactive polysaccharide-containing fraction (AAWAP) was obtained from Artemisia argyi leaves via bioactivity-guided fractionation.•The water extract of A.argyi leaves showed selectively inhibitory effect on podoplanin/tumor cells-induced platelet aggregation.•AAWAP was non-toxic to cells and suppressed PDPN- and tumor cell-induced platelet aggregation.•AAWAP suppressed PDPN- and tumor cell-induced platelet aggregation by irreversibly blocking PDPN-CLEC-2 interaction.