A novelly synthesized phenanthroline derivative is a promising DNA-damaging anticancer agent inhibiting G1/S checkpoint transition and inducing cell apoptosis in cancer cells
A novelly synthesized phenanthroline derivative is a promising DNA-damaging anticancer agent inhibiting G1/S checkpoint transition and inducing cell apoptosis in cancer cells
复制标题
一种新合成的菲咯啉衍生物是一种有前途的 DNA 损伤性抗癌剂，可抑制 G1/S 检查点转换并诱导癌细胞凋亡
DOI：
10.1007/s00280-015-2894-5
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发表时间：
2016-01-01
影响因子：
3
通讯作者：
Yu, Yongchun
中科院分区：
文献类型：
--
作者：
Zhen, Ni;Yang, Qingyuan;Yu, Yongchun
目的研究一种新合成的菲并咪唑衍生物L233的生物学功能，并探讨其可能的作用机制。方法采用MTT法检测细胞存活率，彗星试验检测L233对DNA的损伤作用。此外，还采用免疫印迹法和免疫荧光法检测DNA损伤标志物。流式细胞仪检测L233对细胞周期分布的影响。至于L233处理后的细胞凋亡的检测，Hoechst 33342染色，流式细胞术，和蛋白质印迹法都投入practice.ResultsWe发现，L233抑制肿瘤细胞生长更有效和安全比顺铂。L233是一种DNA损伤剂，不仅通过激活ATM/CHK 1信号通路，而且通过靶向CHK 1降低RAP 80和PARP-1的表达，阻断细胞周期G1/S关卡转换，诱导细胞凋亡，从而影响肿瘤细胞DNA损伤修复。
PurposeThe study mainly aimed to determine the biological function of a novelly synthesized phenanthroimidazole derivative, named L233, and to explore its potential mechanisms.MethodsCell survival was examined using the MTT assays, and the DNA-damaging role of L233 was explored using the comet assay. Moreover, the western blotting assays and immunofluorescence assays were used to detect DNA damage biomarkers. Afterward, the flow cytometry was used to assess the effects of L233 on cell cycle distribution. As for the detection of cell apoptosis upon L233 treatment, the Hoechst 33342 staining, flow cytometry, and western blotting assays were all put into practice.ResultsWe find that L233 inhibits tumor cell growth more efficiently and safely than cisplatin. Moreover, it is a DNA-damaging agent, interrupting the cell cycle G1/S checkpoint transition and inducing cell apoptosis by not only activating ATM/CHK1 signaling pathway, but also targeting CHK1 to reduce the expression of RAP80 and PARP-1 to compromise the DNA damage repair in tumor cells.ConclusionsIn summary, L233 is a promising anticancer drug for the development of novel chemotherapies in the future.