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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/7528


    Title: Attenuation of argininosuccinate lyase inhibits cancer growth via cyclin A2 and nitric oxide
    Authors: Huang, HL;Hsu, HP;Shieh, SC;Chang, YS;Chen, WC;Cho, CY;Teng, CF;Su, IJ;Hung, WC;Lai, MD
    Contributors: Division of Infectious Diseases;National Institute of Cancer Research
    Abstract: Arginine biosynthesis and nitric oxide (NO) production are important for cancer homeostasis. Degradation of arginine may be employed to inhibit liver tumors with low argininosuccinate synthetase expression. In this report, we investigated an alternative therapeutic approach by targeting argininosuccinate lyase (ASL). ASL is transcriptionally induced by endoplasmic reticulum stress and is overexpressed in some human liver tumors. Knockdown of ASL expression by shRNA in three liver cancer cell lines, ML-1, HuH-7, and HepG2, decreased colony formation in vitro and tumor growth in vivo. Furthermore, lentiviral infection of ASL shRNA inhibited tumor growth in a therapeutic animal tumor model. Analysis of ASL shRNA on the cell cycle progression revealed a G2/M delay. Among cell-cycle regulatory molecules, cyclin A2 expression was reduced. Reintroduction of exogenous cyclin A2 restored the cell growth in ASL-knockdown cells. Autophagy was observed in the cells treated with ASL shRNA, as demonstrated by an increase in LC3-II levels and autophagosome formation. The total cellular arginine level was not altered significantly. Inhibition of autophagy further attenuated cell growth, suggesting that autophagy induced by ASL shRNA plays a feedback pro-survival function. Knockdown of ASL reduced NO content, and addition of NO donor partially recovered the growth inhibition by ASL shRNA. In summary, downregulation of ASL attenuated tumor growth and the inhibition was mainly mediated by a decrease of cyclin A2 and NO.
    Date: 2013-11
    Relation: Molecular Cancer Therapeutics. 2013 Nov;12(11):2505-2516.
    Link to: http://dx.doi.org/10.1158/1535-7163.mct-12-0863
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1535-7163&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000326886000020
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84887455091
    Appears in Collections:[蘇益仁(2002-2015)] 期刊論文
    [洪文俊] 期刊論文

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