A novel topoisomerase 2a inhibitor, cryptotanshinone, suppresses the growth of PC3 cells without apparent cytotoxicity

被引:12
作者
Kim, Eun Ju [1 ,2 ]
Kim, Sun Young [1 ]
Kim, Sang-Man [2 ]
Lee, Minyoung [1 ]
机构
[1] Korea Inst Radiol & Med Sci, Div Radiat Effect, Seoul 01812, South Korea
[2] Kyung Hee Univ, KH Sch Management, Hlth Serv Management, Seoul 02453, South Korea
基金
新加坡国家研究基金会;
关键词
Topoisomerase; Chemotherapeutic agent; Cleavable complex; Cryptotanshinone; Human prostate cancer; II-ALPHA EXPRESSION; ENZYME; BETA; POISONS;
D O I
10.1016/j.taap.2017.07.007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
DNA topoisomerase 2, which is ubiquitously expressed in eukaryotic cells, is an essential nuclear enzyme that promotes cell survival by regulating DNA topology and chromatid separation. This enzyme has been validated as a target for anticancer agent screening. It can be poisoned by common chemotherapeutics, such as etoposide and doxorubicin, which leads to the accumulation of cytotoxic enzyme-linked DNA double-stranded breaks. However, recent studies have suggested that the topoisomerase 2a isozyme is predominantly responsible for the carcinogenic side effects associated with etoposide and doxorubicin chemotherapy. Thus, we need to find a promising topoisomerase 2-targeting anticancer agent that avoids these carcinogenic side effects. Recent studies have found that cryptotanshinone has obvious anticancer activities against diverse cancer cells. Here, we demonstrate that cryptotanshinone markedly decreases the steady-state mRNA level of topoisomerase 2a, thereby decreasing the protein and activity levels of this enzyme. Moreover, cryptotanshinone exhibited dramatic in vitro and in vivo antitumor activity with low toxicity to normal tissues. Collectively, our findings support the development of cryptotanshinone as a promising candidate for treating cancer by targeting topoisomerase 2a. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:84 / 92
页数:9
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