QS-ZYX-1-61 induces apoptosis through topoisomerase II in human non-small-cell lung cancer A549 cells

Mei Chuan Chen, Shiow Lin Pan, Qian Shi, Zhiyan Xiao, Kuo Hsiung Lee, Tsai Kun Li, Che Ming Teng

研究成果: 雜誌貢獻文章同行評審

12 引文 斯高帕斯(Scopus)

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 VP-16 in suppressing the viability of A549 cells. Treatment of cells with QS-ZYX-1-61 led to a DNA damage response 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 IIα, and topo IIβ greatly protected against caspase-3 activation, poly-ADP-ribose polymerase cleavage, and cell growth inhibition, indicating that QS-ZYX-1-61 acts through these proteins. These results support our conclusion that QS-ZYX-1-61has potential as an anticancer agent because it causes accumulation of DNA cleavable complexes, with downstream consequences that include double-strand breaks and DNA damage response 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.
原文英語
頁(從 - 到)80-87
頁數8
期刊Cancer Science
103
發行號1
DOIs
出版狀態已發佈 - 一月 2012
對外發佈

ASJC Scopus subject areas

  • 癌症研究
  • 腫瘤科

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