國家衛生研究院 NHRI:Item 3990099045/5968
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    题名: QS-ZYX-1-61 induces apoptosis through topoisomerase II in human non-small-cell lung cancer A549 cells
    作者: Chen, MC;Pan, SL;Shi, Q;Xiao, Z;Lee, KH;Li, TK;Teng, CM
    贡献者: Institute of Biotechnology and Pharmaceutical Research
    摘要: Agents that cause DNA damage have been widely used as anticancer drugs because DNA lesions can initiate DNA checkpoints that induce cell death. The results presented here indicate that QS-ZYX-1-61, a derivative of VP-16, was significantly more potent than etoposide (VP-16) in suppressing the viability of A549 cells. Treatment of cells with QS-ZYX-1-61 led to a DNA damage response (DDR) and a dramatic increase of apoptosis. Our results also suggest that QS-ZYX-1-61 may be a topoisomerase (topo) II targeting agent as evidenced by relaxation assay and induction of reversible cleavable complexes. Moreover, blocking of p53, topo IIalpha, and topo IIbeta greatly protected against caspase-3 activation, PARP cleavage, and cell growth inhibition, indicating that QS-ZYX-1-61 acts through these proteins. These results support our conclusion that QS-ZYX-1-61 has potential as an anti-cancer agent because it causes accumulation of DNA cleavable complexes, with downstream consequences that include double-strand breaks (DSBs) and DDR signaling for apoptosis. Taken together, our results indicate that QS-ZYX-1-61 is a novel DNA damaging agent and displays an outstanding activity that could be worthy of further investigation.
    日期: 2012-01
    關聯: Cancer Science. 2012 Jan;103(1):80-87.
    Link to: http://dx.doi.org/10.1111/j.1349-7006.2011.02103.x
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1347-9032&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000298877600011
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84855517944
    显示于类别:[潘秀玲(2009-2013)] 期刊論文

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