Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
July-2018 Volume 40 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2018 Volume 40 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

ClC-3 chloride channel protein induces G1 arrest in hepatocellular carcinoma Hep3B cells

  • Authors:
    • Rui Wang
    • Bijun Kang
    • Rendong Hu
    • Youwai Huang
    • Zixi Qin
    • Jichen Du
    • Xi Lin
  • View Affiliations / Copyright

    Affiliations: Beijing Key Laboratory of Magnetic Resonance Imaging Technology, Beijing 100191, P.R. China, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Neurology, Aerospace Center Hospital, Peking University Aerospace Clinical College, Beijing 100039, P.R. China
  • Pages: 472-478
    |
    Published online on: May 3, 2018
       https://doi.org/10.3892/or.2018.6416
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

ClC-3 is a type of chloride channel that has multiple functions in tumorigenesis and tumor growth, and can be blocked by DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid). In the present study, we found that DIDS inhibited the proliferation of Hep3B hepatocellular carcinoma (HCC) cells in a concentration-dependent manner. More in-depth research demonstrated that DIDS downregulated the protein expression levels of cyclin D1 and cyclin E, which are key proteins of the G1 phase. Additionally, we found that ClC-3 siRNA transfection induced G1 arrest in the Hep3B cells, confirming that ClC-3 is involved in the DIDS-induced inhibition of Hep3B cells. Moreover, the level of α-fetoprotein (AFP), a negative prognostic indicator of HCC, was decreased after treatment with DIDS and ClC-3 siRNA. In conclusion, we demonstrated that ClC-3 can arrest the cell cycle at the G1 phase to inhibit cell proliferation, suggesting that ClC-3 has the potential to be a novel target for HCC therapy and potentially improve the prognosis of HCC patients.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Zhang Y, Ren JS, Shi JF, Li N, Wang YT, Qu C, Zhang Y and Dai M: International trends in primary liver cancer incidence from 1973 to 2007. BMC Cancer. 15:942015. View Article : Google Scholar : PubMed/NCBI

2 

Park GH, Song HM and Jeong JB: The coffee diterpene kahweol suppresses the cell proliferation by inducing cyclin D1 proteasomal degradation via ERK1/2, JNK and GKS3β-dependent threonine-286 phosphorylation in human colorectal cancer cells. Food Chem Toxicol. 95:142–148. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Yuan C, Zhu X, Han Y, Song C, Liu C, Lu S, Zhang M, Yu F, Peng Z and Zhou C: Elevated HOXA1 expression correlates with accelerated tumor cell proliferation and poor prognosis in gastric cancer partly via cyclin D1. J Exp Clin Cancer Res. 35:152016. View Article : Google Scholar : PubMed/NCBI

4 

Quelle DE, Ashmun RA, Shurtleff SA, Kato JY, Bar-Sagi D, Roussel MF and Sherr CJ: Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes Dev. 7:1559–1571. 1993. View Article : Google Scholar : PubMed/NCBI

5 

Cohen EE, Zhu H, Lingen MW, Martin LE, Kuo WL, Choi EA, Kocherginsky M, Parker JS, Chung CH and Rosner MR: A feed-forward loop involving protein kinase Calpha and microRNAs regulates tumor cell cycle. Cancer Res. 69:65–74. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Jin DH, Kim Y, Lee BB, Han J, Kim HK, Shim YM and Kim DH: Metformin induces cell cycle arrest at the G1 phase through E2F8 suppression in lung cancer cells. Oncotarget. 8:101509–101519. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Amorim R, Pinheiro C, Miranda-Gonçalves V, Pereira H, Moyer MP, Preto A and Baltazar F: Monocarboxylate transport inhibition potentiates the cytotoxic effect of 5-fluorouracil in colorectal cancer cells. Cancer Lett. 365:68–78. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Li M, Wang Q, Lin W and Wang B: Regulation of ovarian cancer cell adhesion and invasion by chloride channels. Int J Gynecol Cancer. 19:526–530. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Kang MK and Kang SK: Pharmacologic blockade of chloride channel synergistically enhances apoptosis of chemotherapeutic drug-resistant cancer stem cells. Biochem Biophys Res Commun. 373:539–544. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Kunzelmann K: Ion channels and cancer. J Membr Biol. 205:159–173. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Arcangeli A, Crociani O, Lastraioli E, Masi A, Pillozzi S and Becchetti A: Targeting ion channels in cancer: A novel frontier in antineoplastic therapy. Curr Med Chem. 16:66–93. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Conti M: Targeting ion channels for new strategies in cancer diagnosis and therapy. Curr Clin Pharmacol. 2:135–144. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Guan YY, Wang GL and Zhou JG: The ClC-3 Cl− channel in cell volume regulation, proliferation and apoptosis in vascular smooth muscle cells. Trends Pharmacol Sci. 27:290–296. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Lemonnier L, Shuba Y, Crepin A, Roudbaraki M, Slomianny C, Mauroy B, Nilius B, Prevarskaya N and Skryma R: Bcl-2-dependent modulation of swelling-activated Cl− current and CLC-3 expression in human prostate cancer epithelial cells. Cancer Res. 64:4841–4848. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Weylandt KH, Nebrig M, Jansen-Rosseck N, Amey JS, Carmena D, Wiedenmann B, Higgins CF and Sardini A: ClC-3 expression enhances etoposide resistance by increasing acidification of the late endocytic compartment. Mol Cancer Ther. 6:979–986. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Su J, Xu Y, Zhou L, Yu HM, Kang JS, Liu N, Quan CS and Sun LK: Suppression of chloride channel 3 expression facilitates sensitivity of human glioma U251 cells to cisplatin through concomitant inhibition of Akt and autophagy. Anat Rec. 296:595–603. 2013. View Article : Google Scholar

17 

Xu Y, Zheng H, Kang JS, Zhang L, Su J, Li HY and Sun LK: 5-Nitro-2-(3-phenylpropylamino) benzoic acid induced drug resistance to cisplatin in human erythroleukemia cell lines. Anat Rec. 294:945–952. 2011. View Article : Google Scholar

18 

Du S and Yang L: ClC-3 chloride channel modulates the proliferation and migration of osteosarcoma cells via AKT/GSK3β signaling pathway. Int J Clin Exp Pathol. 8:1622–1630. 2015.PubMed/NCBI

19 

Bruix J and Sherman M: Practice Guidelines Committee, American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma. Hepatology. 42:1208–1236. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Bruix J and Sherman M: American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma: An update. Hepatology. 53:1020–1022. 2011. View Article : Google Scholar : PubMed/NCBI

21 

European Association For The Study Of The LiverEuropean Organisation For Research And Treatment Of Cancer: EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol. 56:908–943. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Chan SL, Mo FK, Johnson PJ, Hui EP, Ma BB, Ho WM, Lam KC, Chan AT, Mok TS and Yeo W: New utility of an old marker: Serial alpha-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy. J Clin Oncol. 27:446–452. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Keam B, Oh DY, Lee SH, Kim DW, Im SA, Kim TY, Heo DS and Bang YJ: A phase II study of 5-fluorouracil and cisplatin systemic chemotherapy for inoperable hepatocellular carcinoma with α fetoprotein as a predictive and prognostic marker. Mol Med Rep. 1:415–422. 2008.PubMed/NCBI

24 

Ye D, Luo H, Lai Z, Zou L, Zhu L, Mao J, Jacob T, Ye W, Wang L and Chen L: ClC-3 Chloride Channel Proteins Regulate the Cell Cycle by Up-regulating cyclin D1-CDK4/6 through Suppressing p21/p27 Expression in Nasopharyngeal Carcinoma Cells. Sci Rep. 6:302762016. View Article : Google Scholar : PubMed/NCBI

25 

Wondergem R, Gong W, Monen SH, Dooley SN, Gonce JL, Conner TD, Houser M, Ecay TW and Ferslew KE: Blocking swelling-activated chloride current inhibits mouse liver cell proliferation. J Physiol. 532:661–672. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Ji X, Shen Y, Sun H and Gao X: A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel. Tumour Biol. 37:10085–10096. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Zhang L, He T, Cui H, Wang Y, Huang C and Han F: Effects of AFP gene silencing on apoptosis and proliferation of a hepatocellular carcinoma cell line. Discov Med. 14:115–124. 2012.PubMed/NCBI

28 

Yu WF, Zhao YL, Wang K and Dong MM: Inhibition of cell proliferation and arrest of cell cycle progression by blocking chloride channels in human laryngeal cancer cell line Hep-2. Neoplasma. 56:224–229. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Wang B, Xie J, He HY, Huang EW, Cao QH, Luo L, Liao YS and Guo Y: Suppression of CLC-3 chloride channel reduces the aggressiveness of glioma through inhibiting nuclear factor-κB pathway. Oncotarget. 8:63788–63798. 2017.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang R, Kang B, Hu R, Huang Y, Qin Z, Du J and Lin X: ClC-3 chloride channel protein induces G1 arrest in hepatocellular carcinoma Hep3B cells. Oncol Rep 40: 472-478, 2018.
APA
Wang, R., Kang, B., Hu, R., Huang, Y., Qin, Z., Du, J., & Lin, X. (2018). ClC-3 chloride channel protein induces G1 arrest in hepatocellular carcinoma Hep3B cells. Oncology Reports, 40, 472-478. https://doi.org/10.3892/or.2018.6416
MLA
Wang, R., Kang, B., Hu, R., Huang, Y., Qin, Z., Du, J., Lin, X."ClC-3 chloride channel protein induces G1 arrest in hepatocellular carcinoma Hep3B cells". Oncology Reports 40.1 (2018): 472-478.
Chicago
Wang, R., Kang, B., Hu, R., Huang, Y., Qin, Z., Du, J., Lin, X."ClC-3 chloride channel protein induces G1 arrest in hepatocellular carcinoma Hep3B cells". Oncology Reports 40, no. 1 (2018): 472-478. https://doi.org/10.3892/or.2018.6416
Copy and paste a formatted citation
x
Spandidos Publications style
Wang R, Kang B, Hu R, Huang Y, Qin Z, Du J and Lin X: ClC-3 chloride channel protein induces G1 arrest in hepatocellular carcinoma Hep3B cells. Oncol Rep 40: 472-478, 2018.
APA
Wang, R., Kang, B., Hu, R., Huang, Y., Qin, Z., Du, J., & Lin, X. (2018). ClC-3 chloride channel protein induces G1 arrest in hepatocellular carcinoma Hep3B cells. Oncology Reports, 40, 472-478. https://doi.org/10.3892/or.2018.6416
MLA
Wang, R., Kang, B., Hu, R., Huang, Y., Qin, Z., Du, J., Lin, X."ClC-3 chloride channel protein induces G1 arrest in hepatocellular carcinoma Hep3B cells". Oncology Reports 40.1 (2018): 472-478.
Chicago
Wang, R., Kang, B., Hu, R., Huang, Y., Qin, Z., Du, J., Lin, X."ClC-3 chloride channel protein induces G1 arrest in hepatocellular carcinoma Hep3B cells". Oncology Reports 40, no. 1 (2018): 472-478. https://doi.org/10.3892/or.2018.6416
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team