Evidence shows that polysaccharides in Traditional Chinese Medicine have the bioactivities in immune modulation, anti-cancer, anti-virus, anti-coagulant and even in diabetes treat. However, the mechanism underlying the polysaccharides bioactivities is not clear. For those people who lack basic background about polysaccharides even think polysaccharide has no specificity and clear target on the bioactivity. These points of view hamper the polysaccharide-based drug development over a long period in China.

Fig. 1. Structural diagram of WSS25

Fig 2. Effects of WSS25 on Id1, BMP2 and Smad signaling pathway components. A, WSS25 bound BMP2; B, WSS25 displayed different effects on the expressions of BMP2, BMPRIA, BMPRIB, BMPRII, and Smad4; B, WSS25 or noggin inhibited both Smad1/5/8 phosphorylation and Id1 expression in HMEC-1 cells induced by BMP2.

 

Hepatomacellular carcinoma (HCC) is the second most lethal malignant cancer in China and causes about 600,000 death each year. It’s still a good way to inhibit tumor growth by blocking angiogenesis in HCC. However, drug resistance has been reported when anti-angiogenesis inhibitor is used in the clinic. Therefore, it’s a hot spot to find high efficient anti-angiogenesis inhibitor with low toxicity and less drug resistance.
Research group lead by Prof. Kan Ding, Glycobiology & Glycochemistry lab in Shanghai Institute of Materia Medica (SIMM) focuses on the study on the anti-tumor mechanism of polysaccharide. The polysaccharide was extracted from Traditional Chinese Medicine Gastrodia elata Bl and then purified and sulphated to get compound WSS25. By targeting BMP2 and its receptors, WSS25 blocked BMP/SMAD/ID1 signaling pathway and disrupted angiogenesis and inhibited the growth of HCC in vivo. The results have been published online on Journal of Biological Chemistry, 2010, (doi:10.1074/jbc. M110.105544).
The highly expressed Id1 (inhibitor of DNA binding/differentiation) protein promotes angiogenesis in HCC and is a wellestablished target for anti-angiogenesis therapeutic strategies. Some sulfate polysaccharides (HS) can abrogate HS-protein interactions to inhibit angiogenesis. The HS mimetics WSS25 inhibit angiogenesis via attenuating Id1 expression and blocked BMP/Smad/Id1 signaling pathway. The quartz crystal microbalance (QCM) analysis showed that WSS25 strongly bound toBMP2 and abrogated the growth of HCC cells xenografted in male nude mice. Therefore, WSS25 is a potential drug candidate for HCC therapy as a tumor angiogenesis inhibitor. The mechanism study provides the foundation for WSS25-based anti-tumor new drug development.
The research work was mainly accomplished by Dr. Hong Qiu in this lab. This program is supported by The People's Republic of China Ministry of Science and Technology, the National Natural Science Foundation of China and Chinese Academy of Sciences.