当前位置： SCI文献检索 > CANCER CHEMOTHERAPY AND PHARMACOLOGY期刊下所有文献 > 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.

Abstract：

PURPOSE:The study mainly aimed to determine the biological function of a novelly synthesized phenanthroimidazole derivative, named L233, and to explore its potential mechanisms. METHODS:Cell 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. RESULTS:We 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. CONCLUSIONS:In summary, L233 is a promising anticancer drug for the development of novel chemotherapies in the future.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Zhen N,Yang Q,Wu Q,Zhu X,Wang Y,Sun F,Mei W,Yu Y

doi

10.1007/s00280-015-2894-5

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

169-80

issue

1

eissn

0344-5704

issn

1432-0843

pii

10.1007/s00280-015-2894-5

journal_volume

77

pub_type

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