8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A quantitative proteomic response of hepatocellular carcinoma Hep3B cells to danusertib, a pan-Aurora kinase inhibitor

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, but the overall prognosis remains disappointing especially in the advanced-stage patients. Aberration expression of Aurora kinases is tumorigenic and thus it has attracted interests as therapeutic targets in cancer treatment. Here, we investigated the proteomic response of HCC Hep3B cells to danusertib (Danu), a pan-Aurora kinase inhibitor, and then validated the proteomic results based on stable-isotope labeling by amino acids in cell culture (SILAC). The proteomic data identified that Danu modulated the expression of 542 protein molecules (279 up-regulated; 260 down-regulated; 3 stable). Ingenuity pathway analysis (IPA) and KEGG pathway analysis identified 107 and 24 signaling pathways were regulated by Danu, respectively. IPA analysis showed cellular growth and proliferation, and cell death and survival were among the top five molecular and cellular functions regulated by Danu. The verification experiments showed that Danu inhibited the proliferation of Hep3B cells with a 24-hr IC 50 value of 22.03 µM. Danu treatment also arrested Hep3B cells in G 2/M phase via regulating the expression of key cell cycle regulators and induced apoptosis via mitochondria-dependent pathway in a dose-dependent manner. Besides, Danu induced a marked autophagy, and inhibition of autophagy enhanced the anticancer effects of Danu, indicating a cyto-protective role of Danu-induced autophagy. Our proteomic data and Western blotting assays showed the PI3K/Akt/mTOR signaling pathway was involved in the inducing effect of Danu on apoptosis and autophagy. Collectively, our findings have demonstrated that the Aurora kinases inhibition with danusertib results in global proteomic response and exerts anticancer effects in Hep3B cells involving regulation of cell cycle, apoptosis and autophagy and associated signaling pathways.

          Related collections

          Most cited references41

          • Record: found
          • Abstract: found
          • Article: not found

          Cell cycle proteins as promising targets in cancer therapy

          Cancer is characterized by uncontrolled tumour cell proliferation resulting from aberrant activity of various cell cycle proteins. Therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrate that some of these proteins are not essential for proliferation of non-transformed cells
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The diagnosis and treatment of hepatocellular carcinoma.

            Hepatocellular carcinoma is a leading cancer worldwide. Its incidence is increasing, and is closely related to advanced liver disease. Cirrhosis represents the greatest risk factor for this malignancy, and is the main indication for screening and surveillance. The diagnosis of hepatocellular carcinoma can frequently, and uniquely, be made on characteristic multiphase contrast based cross-sectional imaging rather than strict need for tissue sampling. Despite advances in medical, locoregional and surgical therapies, hepatocellular carcinoma remains one of the most common causes of cancer-related death globally. In this review, current approaches to management of hepatocellular carcinoma are discussed, which incorporate both tumor and patient factors. The salient considerations in surgical (resection, liver transplantation), locoregional (ablation and embolic therapies) and medical therapies are highlighted.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Hepatocellular carcinoma (HCC): beyond sorafenib-chemotherapy.

              Hepatocellular carcinoma (HCC) is the most common primary liver cancer with poor prognosis. The incidence of HCC and HCC-related deaths have increased over the last several decades. However, the treatment options for advanced HCC are very limited. Sorafenib remains the only drug approved for systemic treatment for advanced HCC. However, prior to sorafenib era conventional cytotoxic chemotherapies have been studied in advanced HCC. In this review, clinical studies of systemic chemotherapy for advanced HCC will be summarized and discussed.
                Bookmark

                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2018
                24 May 2018
                : 9
                : 12
                : 2061-2071
                Affiliations
                [1 ]Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, Guangdong 510515, China.
                [2 ]Department of Oncology and Interventional Radiology, Shunde Hospital, Southern Medical University, Shunde, Foshan, Guangdong 528300, China
                [3 ]Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA.
                [4 ]Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center & Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang 550004, China.
                [5 ]Department of Bioengineering and Biotechnology, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian 361021, China.
                Author notes
                ✉ Corresponding authors: Professor Shu-Feng Zhou, MD & PhD, Department of Bioengineering and Biotechnology, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian 361021, China. Tel: +86 592 6162288; Fax: +86 592 6162300; Email: szhou@ 123456hqu.edu.cn and Professor Yong Chen, MD, Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, 1838, North Guangzhou Avenue, Guangzhou City, Guangdong 510515, China. Email: cheny102@ 123456163.com .

                #These two authors contribute equally to this article.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav09p2061
                10.7150/jca.20822
                6010685
                29937924
                39349fc9-026a-45a2-80e4-c3fea28cfbbb
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 2 May 2017
                : 16 February 2018
                Categories
                Research Paper

                Oncology & Radiotherapy
                hepatocellular carcinoma,aurora kinases,danusertib,cell cycle,apoptosis,autophagy, quantitative proteomics.

                Comments

                Comment on this article