Lipid Raft Stationary Phase Chromatography for Screening Anti-tumor Components from Galla chinensis

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• 作者：Shanshan Tong (1)
  Min Fu (1)
  Xia Cao (1)
  Caleb Kesse Firempong (1)
  Chengxue Yi (1)
  Qianfeng Zhen (1)
  Hui Zhong (1)
  Jiangnan Yu (1)
  Ximing Xu (1)
  
• 关键词：Lipid raft stationary phase chromatography ; Anti ; tumor experimental therapeutics ; Drug screening ; Chinese traditional medicine ; Chinese gallnut
• 刊名：Chromatographia
• 出版年：2014
• 出版时间：March 2014
• 年：2014
• 卷：77
• 期：5-6
• 页码：419-429
• 全文大小：792 KB
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• 作者单位：Shanshan Tong (1)
  Min Fu (1)
  Xia Cao (1)
  Caleb Kesse Firempong (1)
  Chengxue Yi (1)
  Qianfeng Zhen (1)
  Hui Zhong (1)
  Jiangnan Yu (1)
  Ximing Xu (1)
  
  1. Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, 212013, People’s Republic of China
  
• ISSN：1612-1112

文摘

For the first time, a novel biological affinity separating system called lipid raft stationary phase chromatography (LRSC) was developed. It was employed to screen bioactive components from Chinese gallnut, a traditional Chinese medicine (TCM). The LRSC was prepared by the addition of activated silica to Tris–HCl solution, which contains the isolated lipid rafts of U251 cells. This was followed by agitation, washing, centrifugation and then re-suspension of the residue in another Tris–HCl solution. The lipid rafts possess abundant receptor tyrosine kinase, specifically tropomyosin-related kinase A (TrkA), which is a widely researched anti-tumor drug target. Thus, TrkA provided the LRSC model with the ability to select fractions that specifically interact with it. Using a non-TrkA targeted anti-tumor drug (gemcitabine) and TrkA targeted anti-tumor drugs (lestaurtinib and gefitinib) as controls to evaluate the specific affinity of the LRSC column, the different fractions of Chinese gallnut were subjected to LRSC screening for the identification of anti-tumor components. As a result, the ether fraction of Chinese gallnut manifested desirable affinity properties. The methyl thiazolyl tetrazolium assay confirmed the anti-tumor effect of the screened ether fraction, and more importantly, the ether fraction failed woefully to exhibit its anti-proliferative activity in the presence of TrkA inhibitors (K252a and primary antibody). This further proves the selectivity of LRSC on TrkA-targeted drugs. The LRSC model has, therefore, shown to be of high efficiency and selectivity in screening bioactive components from the complex TCM extracts, thus offering an effective approach for the development of anticancer natural products.