Beclin1 affected by DN604 upregulates chemo-sensitivity of cervix SiHa cancer cells via inhibiting CK2-MRN-DSBs repairChen, Feihong; Sun, Shuchen; Liu, Nannan; Pei, Sinan; Zhu, Qian; Wang, Xinyi; Gou, ShaohuaAnti-Cancer Drugs: September 2019 - Volume 30 - Issue 8 - p 774–783 doi: 10.1097/CAD.0000000000000804 Preclinical Papers Buy SDC Abstract Author InformationAuthors Article MetricsMetrics 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 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.anti-cancerdrugs.com. Correspondence to Shaohua Gou, Dongnandaxue Road 2#, Jiangning District, Southeast University, Nanjing, China, Tel: +13813839472; fax: 025-52091139; e-mail: firstname.lastname@example.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.