國家衛生研究院 NHRI:Item 3990099045/9780

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Title:	Active component isolated from human urine extract (CDA-2) has activities of eliminating cancer stem-like cells and inhibition of epithelial mesenchymal transition
Authors:	Yao, CJ;Yeh, CT;Yeh, CF;Chang, CK;Li, CH;Yan, JL;Chuang, SE;Lai, GM
Contributors:	National Institute of Cancer Research
Abstract:	Recently, the concept of \#8220;cancer stem cell\#8221; may renew the notion of designing cancer therapy. The progression and relapse of tumor may be initiated by the remaining cancer stem cells that escaped from conventional cancer treatments such as chemotherapy and radiation. The research for therapeutics targeting this small population of cancer stem cells is badly needed. By UV laser equipped flow cytometer and cell-permeable DNA binding dye Hoechst 33342, a distinct side population (SP) cells expressing high-level of ATP-binding cassette transporter protein ABCG2/Bcrp1, could be identified and sorted. These SP cells possess characteristics of stem cells such as self renewal and expression of stemness genes. Using this stem-like SP cells as a model, our previous studies had found that a human urine extract CDA-2 could eliminate SP cells in Huh7 hepatoma cells and down-regulate the expression of stemness genes such as CD133, SMO, Oct-4 and \#946;-catenin. In addition, CDA-2 was also found to inhibit the EGF-induced epithelial-mesenchymal transition (EMT) in A549 lung cancer cells. Therefore, it is interesting to find any active component from CDA-2 that plays the key role. After solvent extraction and HPLC separation, a peak in the HPLC profile named as P23.2 was found to possess the activities of SP cell elimination and EMT inhibition. After 48 h incubation with Huh7 hepatoma cells, the percentage of SP cells was decreased from 1.26% to 0.17% by CDA-2 at dose of 4 mg/ml, in contrast, P23.2 reduced the SP cells from 1.69% to 0.18% at dose of 25 \#956;g/ml, indicating the P23.2 was about 160 times more potent than CDA-2. Moreover, the P23.2 also exerted inhibitory effects on the EGF-induced EMT in A549 lung cancer cells as that did by CDA-2. Not only the mesenchymal-like morphologic changes but also the decreased epithelial marker E-cadherin and the elevated Snail (E-cadherin repressor) m-RNA expressions were almost completely reversed by 50 \#956;g/ml of P23.2. These results indicate the existence of active component in human urine, which may have the potential for cancer control. Further identification and subsequent modification of chemical structure of P23.2 as novel therapeutic is warranted.
Date:	2009-05
Relation:	Cancer Research. 2009 May;69:Abstract number 5461.
Link to:	http://cancerres.aacrjournals.org/content/69/9_Supplement/5461.short
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000209702704465
Appears in Collections:	[Gi-Ming Lai(2004-2008)] Conference Papers/Meeting Abstract [Shuang-En Chuang] Conference Papers/Meeting Abstract

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