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
November-2017 Volume 38 Issue 5

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
November-2017 Volume 38 Issue 5

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

Celastrol downregulates E2F1 to induce growth inhibitory effects in hepatocellular carcinoma HepG2 cells

  • Authors:
    • Liang Ma
    • Lei Peng
    • Sheng Fang
    • Bangguo He
    • Zi Liu
  • View Affiliations / Copyright

    Affiliations: Department of Chemical Biology and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma'anshan, Anhui 243002, P.R. China
  • Pages: 2951-2958
    |
    Published online on: September 19, 2017
       https://doi.org/10.3892/or.2017.5971
  • 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

Celastrol, a natural compound extracted from Tripterygium wilfordii, is known to exhibit potential anticancer activities in various types of tumor cells. E2F1 is reported to be overexpressed in several types of human tumors and its inactivation may be a valuable novel potential therapeutic strategy for cancer treatment. However, the molecular mechanism underlying the pro-apoptotic effects of celastrol on hepatocellular carcinoma (HCC) cells remains unclear, and E2F1-targeted compounds have been rarely identified. In the present study, we demonstrated that celastrol inhibited the proliferation of human HCC cells and triggered apoptosis of HepG2 cells in a caspase-dependent manner. E2F1 was potently downregulated by celastrol in a dose- and time-dependent manner at both the mRNA and protein levels. Moreover, siRNA-mediated E2F1 silencing enhanced celastrol-induced apoptosis and inhibition of proliferation. Our data imply that downregulation of E2F1 may be a key factor in the celastrol-mediated inhibitory effects in HepG2 cells, and celastrol can serve as a leading compound for the development of compounds designed to inactivate E2F1 for HCC therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Attwa MH and El-Etreby SA: Guide for diagnosis and treatment of hepatocellular carcinoma. World J Hepatol. 7:1632–1651. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al SHARP Investigators Study Group, : Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Thorgeirsson SS and Grisham JW: Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet. 31:339–346. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Nakajima T, Yasui K, Zen K, Inagaki Y, Fujii H, Minami M, Tanaka S, Taniwaki M, Itoh Y, Arii S, et al: Activation of B-Myb by E2F1 in hepatocellular carcinoma. Hepatol Res. 38:886–895. 2008.PubMed/NCBI

5 

Pagliarini V, Giglio P, Bernardoni P, De Zio D, Fimia GM, Piacentini M and Corazzari M: Downregulation of E2F1 during ER stress is required to induce apoptosis. J Cell Sci. 128:1166–1179. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Rajendran P, Li F, Shanmugam MK, Kannaiyan R, Goh JN, Wong KF, Wang W, Khin E, Tergaonkar V, Kumar AP, et al: Celastrol suppresses growth and induces apoptosis of human hepatocellular carcinoma through the modulation of STAT3/JAK2 signaling cascade in vitro and in vivo. Cancer Prev Res. 5:631–643. 2012. View Article : Google Scholar

7 

Feng L, Zhang D, Fan C, Ma C, Yang W, Meng Y, Wu W, Guan S, Jiang B, Yang M, et al: ER stress-mediated apoptosis induced by celastrol in cancer cells and important role of glycogen synthase kinase-3β in the signal network. Cell Death Dis. 4:e7152013. View Article : Google Scholar : PubMed/NCBI

8 

Fribley AM, Miller JR, Brownell AL, Garshott DM, Zeng Q, Reist TE, Narula N, Cai P, Xi Y, Callaghan MU, et al: Celastrol induces unfolded protein response-dependent cell death in head and neck cancer. Exp Cell Res. 330:412–422. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Ma L, Wen ZS, Liu Z, Hu Z, Ma J, Chen XQ, Liu YQ, Pu JX, Xiao WL, Sun HD, et al: Overexpression and small molecule-triggered downregulation of CIP2A in lung cancer. PLoS One. 6:e201592011. View Article : Google Scholar : PubMed/NCBI

10 

Liu Z, Ma L, Wen ZS, Cheng YX and Zhou GB: Ethoxysanguinarine induces inhibitory effects and downregulates CIP2A in lung cancer cells. ACS Med Chem Lett. 5:113–118. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Liu JL, Zeng GZ, Liu XL, Liu YQ, Hu ZG, Liu Y, Tan NH and Zhou GB: Small compound bigelovin exerts inhibitory effects and triggers proteolysis of E2F1 in multiple myeloma cells. Cancer Sci. 104:1697–1704. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Liu Z, Ma L, Wen ZS, Hu Z, Wu FQ, Li W, Liu J and Zhou GB: Cancerous inhibitor of PP2A is targeted by natural compound celastrol for degradation in non-small-cell lung cancer. Carcinogenesis. 35:905–914. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Diefenbach J and Bürkle A: Introduction to poly(ADP-ribose) metabolism. Cell Mol Life Sci. 62:721–730. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Zhao Y, Tan J, Zhuang L, Jiang X, Liu ET and Yu Q: Inhibitors of histone deacetylases target the Rb-E2F1 pathway for apoptosis induction through activation of pro-apoptotic protein Bim. Proc Natl Acad Sci USA. 102:pp. 16090–16095. 2005; View Article : Google Scholar : PubMed/NCBI

15 

Matsumura I, Tanaka H and Kanakura Y: E2F1 and c-Myc in cell growth and death. Cell Cycle. 2:333–338. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Lam SK, Li YY, Zheng CY, Leung LL and Ho JC: E2F1 downregulation by arsenic trioxide in lung adenocarcinoma. Int J Oncol. 45:2033–2043. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Kawate S, Fukusato T, Ohwada S, Watanuki A and Morishita Y: Amplification of c-myc in hepatocellular carcinoma: Correlation with clinicopathologic features, proliferative activity and p53 overexpression. Oncology. 57:157–163. 1999. View Article : Google Scholar : PubMed/NCBI

18 

Ciechanover A: Proteolysis: From the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol. 6:79–87. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Adams J: The proteasome: A suitable antineoplastic target. Nat Rev Cancer. 4:349–360. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Huynh H: Molecularly targeted therapy in hepatocellular carcinoma. Biochem Pharmacol. 80:550–560. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Newman DJ and Giddings LA: Natural products as leads to antitumor drugs. Phytochem Rev. 13:123–137. 2014. View Article : Google Scholar

22 

Liu Z, Ma L and Zhou GB: The main anticancer bullets of the Chinese medicinal herb, thunder god vine. Molecules. 16:5283–5297. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Li PP, He W, Yuan PF, Song SS, Lu JT and Wei W: Celastrol induces mitochondria-mediated apoptosis in hepatocellular carcinoma Bel-7402 cells. Am J Chin Med. 43:137–148. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Yan YY, Guo Y, Zhang W, Ma CG, Zhang YX, Wang C and Wang HX: Celastrol enhanced the anticancer effect of lapatinib in human hepatocellular carcinoma cells in vitro. J BUON. 19:412–418. 2014.PubMed/NCBI

25 

Nicholson DW: Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ. 6:1028–1042. 1999. View Article : Google Scholar : PubMed/NCBI

26 

Johnstone RW, Ruefli AA and Lowe SW: Apoptosis: A link between cancer genetics and chemotherapy. Cell. 108:153–164. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Engelmann D, Knoll S, Ewerth D, Steder M, Stoll A and Pützer BM: Functional interplay between E2F1 and chemotherapeutic drugs defines immediate E2F1 target genes crucial for cancer cell death. Cell Mol Life Sci. 67:931–948. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Conner EA, Lemmer ER, Omori M, Wirth PJ, Factor VM and Thorgeirsson SS: Dual functions of E2F-1 in a transgenic mouse model of liver carcinogenesis. Oncogene. 19:5054–5062. 2000. View Article : Google Scholar : PubMed/NCBI

29 

Rabbani F, Richon VM, Orlow I, Lu ML, Drobnjak M, Dudas M, Charytonowicz E, Dalbagni G and Cordon-Cardo C: Prognostic significance of transcription factor E2F-1 in bladder cancer: Genotypic and phenotypic characterization. J Natl Cancer Inst. 91:874–881. 1999. View Article : Google Scholar : PubMed/NCBI

30 

Zacharatos P, Kotsinas A, Evangelou K, Karakaidos P, Vassiliou LV, Rezaei N, Kyroudi A, Kittas C, Patsouris E, Papavassiliou AG, et al: Distinct expression patterns of the transcription factor E2F-1 in relation to tumour growth parameters in common human carcinomas. J Pathol. 203:744–753. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Engelmann D and Pützer BM: The dark side of E2F1: In transit beyond apoptosis. Cancer Res. 72:571–575. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Wu LC, Wen ZS, Qiu YT, Chen XQ, Chen HB, Wei MM, Liu Z, Jiang S and Zhou GB: Largazole arrests cell cycle at G1 phase and triggers proteasomal degradation of E2F1 in lung cancer cells. ACS Med Chem Lett. 4:921–926. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Gorgoulis VG, Zacharatos P, Mariatos G, Kotsinas A, Bouda M, Kletsas D, Asimacopoulos PJ, Agnantis N, Kittas C and Papavassiliou AG: Transcription factor E2F-1 acts as a growth-promoting factor and is associated with adverse prognosis in non-small cell lung carcinomas. J Pathol. 198:142–156. 2002. View Article : Google Scholar : PubMed/NCBI

34 

Eymin B, Gazzeri S, Brambilla C and Brambilla E: Distinct pattern of E2F1 expression in human lung tumours: E2F1 is upregulated in small cell lung carcinoma. Oncogene. 20:1678–1687. 2001. View Article : Google Scholar : PubMed/NCBI

35 

Han S, Park K, Bae BN, Kim KH, Kim HJ, Kim YD and Kim HY: E2F1 expression is related with the poor survival of lymph node-positive breast cancer patients treated with fluorouracil, doxorubicin and cyclophosphamide. Breast Cancer Res Treat. 82:11–16. 2003. View Article : Google Scholar : PubMed/NCBI

36 

Zhu H, Yang W, He LJ, Ding WJ, Zheng L, Liao SD, Huang P, Lu W, He QJ and Yang B: Upregulating Noxa by ER stress, celastrol exerts synergistic anti-cancer activity in combination with ABT-737 in human hepatocellular carcinoma cells. PLoS One. 7:e523332012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ma L, Peng L, Fang S, He B and Liu Z: Celastrol downregulates E2F1 to induce growth inhibitory effects in hepatocellular carcinoma HepG2 cells. Oncol Rep 38: 2951-2958, 2017.
APA
Ma, L., Peng, L., Fang, S., He, B., & Liu, Z. (2017). Celastrol downregulates E2F1 to induce growth inhibitory effects in hepatocellular carcinoma HepG2 cells. Oncology Reports, 38, 2951-2958. https://doi.org/10.3892/or.2017.5971
MLA
Ma, L., Peng, L., Fang, S., He, B., Liu, Z."Celastrol downregulates E2F1 to induce growth inhibitory effects in hepatocellular carcinoma HepG2 cells". Oncology Reports 38.5 (2017): 2951-2958.
Chicago
Ma, L., Peng, L., Fang, S., He, B., Liu, Z."Celastrol downregulates E2F1 to induce growth inhibitory effects in hepatocellular carcinoma HepG2 cells". Oncology Reports 38, no. 5 (2017): 2951-2958. https://doi.org/10.3892/or.2017.5971
Copy and paste a formatted citation
x
Spandidos Publications style
Ma L, Peng L, Fang S, He B and Liu Z: Celastrol downregulates E2F1 to induce growth inhibitory effects in hepatocellular carcinoma HepG2 cells. Oncol Rep 38: 2951-2958, 2017.
APA
Ma, L., Peng, L., Fang, S., He, B., & Liu, Z. (2017). Celastrol downregulates E2F1 to induce growth inhibitory effects in hepatocellular carcinoma HepG2 cells. Oncology Reports, 38, 2951-2958. https://doi.org/10.3892/or.2017.5971
MLA
Ma, L., Peng, L., Fang, S., He, B., Liu, Z."Celastrol downregulates E2F1 to induce growth inhibitory effects in hepatocellular carcinoma HepG2 cells". Oncology Reports 38.5 (2017): 2951-2958.
Chicago
Ma, L., Peng, L., Fang, S., He, B., Liu, Z."Celastrol downregulates E2F1 to induce growth inhibitory effects in hepatocellular carcinoma HepG2 cells". Oncology Reports 38, no. 5 (2017): 2951-2958. https://doi.org/10.3892/or.2017.5971
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