HY-1 通过 ATR-Chk1-Cdc25C 和 Weel 通路诱导人结肠癌细胞 G(2)/M 细胞周期停滞。
HY-1 induces G(2)/M cell cycle arrest in human colon cancer cells through the ATR-Chk1-Cdc25C and Weel pathways.
机构信息
Institute of Nautical Medicine, Nantong University, Nantong, China.
出版信息
Cancer Sci. 2013 Aug;104(8):1062-6. doi: 10.1111/cas.12182. Epub 2013 May 15.
Abstract
The novel aroylthiourea analogue of podophyllotoxin HY-1 (4β-[benzoyl-thioureido]-4-deoxypodophyllotoxin) was synthesized in our laboratory with the aim of developing multitargeted DNA topoisomerase II inhibitors. The compound showed significant antiproliferative effects on seven cancer cell lines and induced G2 /M phase arrest in HCT116 cells. Moreover, HY-1 showed a potent inhibitory effect on topoisomerase II-mediated kinetoplast DNA decatenation in a dose-dependent manner. Our results showed that cdc2 phosphorylation and decreased cdc2 kinase acitivity through the ATR-Chk1-Cdc25C and Weel pathways were the central mechanisms for G2 /M phase arrest in human colon cancer cells.
摘要
新型芳酰基硫脲类鬼臼毒素类似物 HY-1（4β-[苯甲酰基-硫脲基]-4-去氧鬼臼毒素）由本实验室合成，目的是开发多靶点 DNA 拓扑异构酶 II 抑制剂。该化合物对七种癌细胞系具有显著的增殖抑制作用，并诱导 HCT116 细胞 G2/M 期阻滞。此外，HY-1 对拓扑异构酶 II 介导的动基体 DNA 解连环具有显著的抑制作用，呈剂量依赖性。我们的结果表明，cdc2 的磷酸化和通过 ATR-Chk1-Cdc25C 和 Weel 途径降低 cdc2 激酶活性是导致人结肠癌细胞 G2/M 期阻滞的中心机制。
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