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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
June-2019 Volume 17 Issue 6

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
June-2019 Volume 17 Issue 6

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

BAY 87‑2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK‑3β activation

  • Authors:
    • Yang‑Ling Li
    • Ming‑Jun Rao
    • Ning‑Yu Zhang
    • Lin‑Wen Wu
    • Neng‑Ming Lin
    • Chong Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Pharmacology, Hangzhou First People's Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China, School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang 310015, P.R. China, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4547-4553
    |
    Published online on: April 18, 2019
       https://doi.org/10.3892/etm.2019.7500
  • 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

Hepatocellular carcinoma (HCC) is associated with some of the highest cancer‑associated mortality rates. Histone deacetylase (HDAC) inhibitors anti‑HCC activities have been shown to promote Snail‑induced metastasis. In the present study, it was shown that BAY 87‑2243, a hypoxia‑inducible transcription factor‑1α inhibitor, could enhance the anti‑HCC effects of HDAC inhibitors, including trichostatin A and vorinostat. In addition, BAY 87‑2243 plus HDAC inhibitors exhibited synergistic cytotoxicity and induced significant cell death in Hep3B cells. Additionally, BAY 87‑2243 combined with HDAC inhibitors‑treated Hep3B cells formed fewer and smaller colonies as compared with either the control or single agent‑treated cells. Furthermore, glycogen synthase kinase‑3β might be involved in the enhanced cell death induced by BAY 87‑2243 plus HDAC inhibitors. The present data also indicated that BAY 87‑2243 combined with HDAC inhibitors could suppress the migration of Hep3B cells, and BAY 87‑2243 could reverse the HDAC inhibitor‑induced Snail activation in Hep3B cells. In conclusion, BAY 87‑2243 combined with HDAC inhibitors might be an attractive chemotherapy strategy for HCC therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Geng Y, Michowski W, Chick JM, Wang YE, Jecrois ME, Sweeney KE, Liu L, Han RC, Ke N, Zagozdzon A, et al: Kinase-independent function of E-type cyclins in liver cancer. Proc Natl Acad Sci USA. 115:1015–1020. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Fu M, Shi W, Li Z and Liu H: Activation of mPTP-dependent mitochondrial apoptosis pathway by a novel pan HDAC inhibitor resminostat in hepatocellular carcinoma cells. Biochem Biophys Res Commun. 477:527–533. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Yang J, Jin X, Yan Y, Shao Y, Pan Y, Roberts LR, Zhang J, Huang H and Jiang J: Inhibiting histone deacetylases suppresses glucose metabolism and hepatocellular carcinoma growth by restoring FBP1 expression. Sci Rep. 7:438642017. View Article : Google Scholar : PubMed/NCBI

4 

Chen T, Gu C, Xue C, Yang T, Zhong Y, Liu S, Nie Y and Yang H: LncRNA-uc002mbe.2 interacting with hnRNPA2B1 Mediates AKT deactivation and p21 Up-regulation induced by trichostatin in liver cancer cells. Front Pharmacol. 8:6692017. View Article : Google Scholar : PubMed/NCBI

5 

West AC and Johnstone RW: New and emerging HDAC inhibitors for cancer treatment. J Clin Invest. 124:30–39. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Zhang J and Zhong Q: Histone deacetylase inhibitors and cell death. Cell Mol Life Sci. 71:3885–3901. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Yuan H, Li AJ, Ma SL, Cui LJ, Wu B, Yin L and Wu MC: Inhibition of autophagy signi fi cantly enhances combination therapy with sorafenib and HDAC inhibitors for human hepatoma cells. World J Gastroenterol. 20:4953–4962. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Yoon CY, Park MJ, Lee JS, Lee SC, Oh JJ, Park H, Chung CW, Abdullajanov MM, Jeong SJ, Hong SK, et al: The histone deacetylase inhibitor trichostatin A synergistically resensitizes a cisplatin resistant human bladder cancer cell line. J Urol. 185:1102–1111. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Li YL, Zhang NY, Hu X, Chen JL, Rao MJ, Wu LW, Li QY, Zhang B, Yan W and Zhang C: Evodiamine induces apoptosis and promotes hepatocellular carcinoma cell death induced by vorinostat via downregulating HIF-1α under hypoxia. Biochem Biophys Res Commun. 498:481–486. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Huang GW, Yang LY and Lu WQ: Expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factor in hepatocellular carcinoma: Impact on neovascularization and survival. World J Gastroenterol. 11:1705–1708. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Ellinghaus P, Heisler I, Unterschemmann K, Haerter M, Beck H, Greschat S, Ehrmann A, Summer H, Flamme I, Oehme F, et al: BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I. Cancer Med. 2:611–624. 2013.PubMed/NCBI

12 

Schöckel L, Glasauer A, Basit F, Bitschar K, Truong H, Erdmann G, Algire C, Hägebarth A, Willems PH, Kopitz C, et al: Targeting mitochondrial complex I using BAY 87-2243 reduces melanoma tumor growth. Cancer Metab. 3:112015. View Article : Google Scholar : PubMed/NCBI

13 

Basit F, van Oppen LM, Schöckel L, Bossenbroek HM, van Emst-de Vries SE, Hermeling JC, Grefte S, Kopitz C, Heroult M, Hgm Willems P and Koopman WJ: Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells. Cell Death Dis. 8:e27162017. View Article : Google Scholar : PubMed/NCBI

14 

Helbig L, Koi L, Brüchner K, Gurtner K, Hess-Stumpp H, Unterschemmann K, Baumann M, Zips D and Yaromina A: BAY 87-2243, a novel inhibitor of hypoxia-induced gene activation, improves local tumor control after fractionated irradiation in a schedule-dependent manner in head and neck human xenografts. Radiat Oncol. 9:2072014. View Article : Google Scholar : PubMed/NCBI

15 

Häcker G: The morphology of apoptosis. Cell Tissue Res. 301:5–17. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Lan Y, Han J, Wang Y, Wang J, Yang G, Li K, Song R, Zheng T, Liang Y, Pan S, et al: STK17B promotes carcinogenesis and metastasis via AKT/GSK-3β/Snail signaling in hepatocellular carcinoma. Cell Death Dis. 9:2362018. View Article : Google Scholar : PubMed/NCBI

17 

Liu L, Dai Y, Chen J, Zeng T, Li Y, Chen L, Zhu YH, Li J, Li Y, Ma S, et al: Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition by way of Akt/GSK-3β/Snail signaling. Hepatology. 59:531–543. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Peinado H, Portillo F and Cano A: Switching on-off Snail: LOXL2 versus GSK3beta. Cell Cycle. 4:1749–1752. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Cassim S, Raymond VA, Dehbidi-Assadzadeh L, Lapierre P and Bilodeau M: Metabolic reprogramming enables hepatocarcinoma cells to efficiently adapt and survive to a nutrient-restricted microenvironment. Cell Cycle. 17:903–916. 2018. View Article : Google Scholar : PubMed/NCBI

20 

Amann T, Maegdefrau U, Hartmann A, Agaimy A, Marienhagen J, Weiss TS, Stoeltzing O, Warnecke C, Schölmerich J, Oefner PJ, et al: GLUT1 expression is increased in hepatocellular carcinoma and promotes tumorigenesis. Am J Pathol. 174:1544–1552. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Kitajima Y and Miyazaki K: The critical impact of HIF-1a on gastric cancer biology. Cancers (Basel). 5:15–26. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Hall JL, Chatham JC, Eldar-Finkelman H and Gibbons GH: Upregulation of glucose metabolism during intimal lesion formation is coupled to the inhibition of vascular smooth muscle cell apoptosis. Role of GSK3beta. Diabetes. 50:1171–1179. 2001. View Article : Google Scholar : PubMed/NCBI

23 

Zhou BP, Deng J, Xia W, Xu J, Li YM, Gunduz M and Hung MC: Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol. 6:931–940. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Liu KY, Wang LT and Hsu SH: Modification of epigenetic histone acetylation in hepatocellular carcinoma. Cancers (Basel). 10(pii): E82018. View Article : Google Scholar : PubMed/NCBI

25 

Lin KT, Wang YW, Chen CT, Ho CM, Su WH and Jou YS: HDAC inhibitors augmented cell migration and metastasis through induction of PKCs leading to identification of low toxicity modalities for combination cancer therapy. Clin Cancer Res. 18:4691–4701. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Xu W, Liu H, Liu ZG, Wang HS, Zhang F, Wang H, Zhang J, Chen JJ, Huang HJ, Tan Y, et al: Histone deacetylase inhibitors upregulate Snail via Smad2/3 phosphorylation and stabilization of Snail to promote metastasis of hepatoma cells. Cancer Lett. 420:1–13. 2018. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li YL, Rao MJ, Zhang NY, Wu LW, Lin NM and Zhang C: BAY 87‑2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK‑3β activation. Exp Ther Med 17: 4547-4553, 2019.
APA
Li, Y., Rao, M., Zhang, N., Wu, L., Lin, N., & Zhang, C. (2019). BAY 87‑2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK‑3β activation. Experimental and Therapeutic Medicine, 17, 4547-4553. https://doi.org/10.3892/etm.2019.7500
MLA
Li, Y., Rao, M., Zhang, N., Wu, L., Lin, N., Zhang, C."BAY 87‑2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK‑3β activation". Experimental and Therapeutic Medicine 17.6 (2019): 4547-4553.
Chicago
Li, Y., Rao, M., Zhang, N., Wu, L., Lin, N., Zhang, C."BAY 87‑2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK‑3β activation". Experimental and Therapeutic Medicine 17, no. 6 (2019): 4547-4553. https://doi.org/10.3892/etm.2019.7500
Copy and paste a formatted citation
x
Spandidos Publications style
Li YL, Rao MJ, Zhang NY, Wu LW, Lin NM and Zhang C: BAY 87‑2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK‑3β activation. Exp Ther Med 17: 4547-4553, 2019.
APA
Li, Y., Rao, M., Zhang, N., Wu, L., Lin, N., & Zhang, C. (2019). BAY 87‑2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK‑3β activation. Experimental and Therapeutic Medicine, 17, 4547-4553. https://doi.org/10.3892/etm.2019.7500
MLA
Li, Y., Rao, M., Zhang, N., Wu, L., Lin, N., Zhang, C."BAY 87‑2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK‑3β activation". Experimental and Therapeutic Medicine 17.6 (2019): 4547-4553.
Chicago
Li, Y., Rao, M., Zhang, N., Wu, L., Lin, N., Zhang, C."BAY 87‑2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK‑3β activation". Experimental and Therapeutic Medicine 17, no. 6 (2019): 4547-4553. https://doi.org/10.3892/etm.2019.7500
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