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Beclin1 affected by DN604 upregulates chemo-sensitivity of cervix SiHa cancer cells via inhibiting CK2-MRN-DSBs repair

Chen, Feihong; Sun, Shuchen; Liu, Nannan; Pei, Sinan; Zhu, Qian; Wang, Xinyi; Gou, Shaohua

doi: 10.1097/CAD.0000000000000804
Preclinical Papers
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DN604, containing a functional dicarboxylato ligand as carboplatin analogue, was significantly studied to explore its potency of antitumour activity. In vitro and in vivo experimental evidence indicated that DN604 exhibited superior antitumor activity than present platinum(II)-based agents in cervix squamous carcinoma SiHa cancer cells. Moreover, DN604 showed negligible toxic effects in vivo as confirmed as Pt accumulation and body weights of mice. Mechanistic studies have shown that DN604 suppressed CK2-mediated MRN complex to improve its antitumor efficacy by promoting DNA double-strand breaks repair. Furthermore, DN604 could inhibit Beclin1 and attenuate CK2-mediated several DSBs repair-related pathways, thus leading to cell apoptosis. Taken together, our research demonstrated that DN604 with the functional dicarboxylato ligand as the leaving group could effectively enhance chemo-sensitivity of SiHa cells to platinum-based agents via suppressing Beclin1 and CK2-mediated MRN-DSBs repair.

Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Department of chemical biology and pharmaceutical engineering, Southeast University, Nanjing, China

Received 12 March 2019 Revised form accepted 21 May 2019

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Correspondence to Shaohua Gou, Dongnandaxue Road 2#, Jiangning District, Southeast University, Nanjing, China, Tel: +13813839472; fax: 025-52091139; e-mail: sgou@seu.edu.cn

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