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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
January-2016 Volume 13 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
January-2016 Volume 13 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

Induction of autophagy by the MG‑132 proteasome inhibitor is associated with endoplasmic reticulum stress in MCF‑7 cells

  • Authors:
    • Wenhua Bao
    • Yiqi Gu
    • La Ta
    • Keren Wang
    • Zheli Xu
  • View Affiliations / Copyright

    Affiliations: Department of Breast Surgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China
  • Pages: 796-804
    |
    Published online on: November 23, 2015
       https://doi.org/10.3892/mmr.2015.4599
  • 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

The aim of the present study was to investigate whether endoplasmic reticulum (ER) stress is involved in MG‑132‑induced autophagy, and to determine the effects of the inhibition of autophagy and ER stress on cell viability following MG‑132 treatment. The proteasome inhibitor, MG‑132, was used to induce autophagy in MCF‑7 cells, and 3‑methyladenine (3‑MA) and salubrinal were used to inhibit autophagy and ER stress, respectively. An MTT assay was used to analyze cell viability. Apoptosis and the cell cycle were analyzed using flow cytometry. The expression levels of apoptosis‑ and ER stress‑associated genes were investigated using western blot and reverse transcription‑quantitative polymerase chain reaction analyses. MG‑132 inhibited cell proliferation, and induced apoptosis and cell cycle arrest at the G2 phase of the cell cycle. Notably, MG‑132 increased the autophagy‑associated conversion of microtubule‑associated protein 1 light chain 3 (LC3)‑I to LC3‑II, which was partially attenuated by the ER stress inhibitor, salubrinal. In addition, MG‑132 inhibited the protein expression of the anti‑apoptotic protein, B‑cell lymphoma (Bcl)‑2, whereas the expression levels of Bcl‑2‑associated X protein and caspase‑3 were upregulated. These effects were enhanced by co‑treatment with either 3‑MA or salubrinal. Furthermore, the mRNA and protein levels of the ER stress‑associated genes, glucose‑regulated protein 78, growth arrest and DNA damage induced gene‑153, and caspase‑12, were upregulated by MG132, and these levels were significantly inhibited by co‑treatment of the cells with salubrinal. Taken together, the results of the present study indicated that the induction of autophagy by the proteasome inhibitor was associated with ER stress in the MCF‑7 cells, and that the inhibition of autophagy or ER stress enhanced MG‑132‑induced apoptosis. These findings suggest the potential application of inhibitors of ER stress and autophagy, in combination with proteasomal inhibitors, for the development of combinatorial targeted cancer therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Rubinsztein DC: The roles of intracellular protein-degradation pathways in neurodegeneration. Nature. 443:780–786. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Hershko A: The ubiquitin system for protein degradation and some of its roles in the control of the cell division cycle. Cell Death Differ. 12:1191–1197. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Momose I, Iijima M, Kawada M and Ikeda D: A new proteasome inhibitor, TP-110, induces apoptosis in human prostate cancer PC-3 cells. Biosci Biotechnol Biochem. 71:1036–1043. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Yang H, Landis-Piwowar KR, Chen D, Milacic V and Dou QP: Natural compounds with proteasome inhibitory activity for cancer prevention and treatment. Curr Protein Pept Sci. 9:227–239. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Fan WH, Hou Y, Meng FK, Wang XF, Luo YN and Ge PF: Proteasome inhibitor MG-132 induces C6 glioma cell apoptosis via oxidative stress. Acta Pharmacol Sin. 32:619–625. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Testa U: Proteasome inhibitors in cancer therapy. Curr Drug Targets. 10:968–981. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Levine B and Kroemer G: Autophagy in the pathogenesis of disease. Cell. 132:27–42. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Shintani T and Klionsky DJ: Autophagy in health and disease: A double-edged sword. Science. 306:990–995. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Ge PF, Zhang JZ, Wang XF, Meng FK, Li WC, Luan YX, Ling F and Luo YN: Inhibition of autophagy induced by proteasome inhibition increases cell death in human SHG-44 glioma cells. Acta Pharmacol Sin. 30:1046–1052. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Zhu K, Dunner K Jr and McConkey DJ: Proteasome inhibitors activate autophagy as a cytoprotective response in human prostate cancer cells. Oncogene. 29:451–462. 2010. View Article : Google Scholar :

11 

Nishikawa T, Tsuno NH, Okaji Y, Shuno Y, Sasaki K, Hongo K, Sunami E, Kitayama J, Takahashi K and Nagawa H: Inhibition of autophagy potentiates sulforaphane-induced apoptosis in human colon cancer cells. Ann Surg Oncol. 17:592–602. 2010. View Article : Google Scholar

12 

Davids LM, Kleemann B, Cooper S and Kidson SH: Melanomas display increased cytoprotection to hypericin-mediated cyto-toxicity through the induction of autophagy. Cell Biol Int. 33:1065–1072. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Katayama M, Kawaguchi T, Berger MS and Pieper RO: DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells. Cell Death Differ. 14:548–558. 2007. View Article : Google Scholar

14 

Li J, Qin Z and Liang Z: The prosurvival role of autophagy in Resveratrol-induced cytotoxicity in human U251 glioma cells. BMC Cancer. 9:2152009. View Article : Google Scholar : PubMed/NCBI

15 

Apel A, Herr I, Schwarz HP, Rodemann HP and Mayer A: Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy. Cancer Res. 68:1485–1494. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Kim KW, Hwang M, Moretti L, Jaboin JJ, Cha YI and Lu B: Autophagy upregulation by inhibitors of caspase-3 and mTOR enhances radiotherapy in a mouse model of lung cancer. Autophagy. 4:659–668. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Vazquez-Martin A, Oliveras-Ferraros C and Menendez JA: Autophagy facilitates the development of breast cancer resistance to the anti-HER2 monoclonal antibody trastuzumab. PloS One. 4:e62512009. View Article : Google Scholar : PubMed/NCBI

18 

Song J, Qu Z, Guo X, Zhao Q, Zhao X, Gao L, Sun K, Shen F, Wu M and Wei L: Hypoxia-induced autophagy contributes to the chemoresistance of hepatocellular carcinoma cells. Autophagy. 5:1131–1144. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Moretti L, Cha YI, Niermann KJ and Lu B: Switch between apoptosis and autophagy: Radiation-induced endoplasmic reticulum stress? Cell Cycle. 6:793–798. 2007. View Article : Google Scholar : PubMed/NCBI

20 

DeGracia DJ and Montie HL: Cerebral ischemia and the unfolded protein response. J Neurochem. 91:1–8. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Kapoor A and Sanyal AJ: Endoplasmic reticulum stress and the unfolded protein response. Clin Liver Dis. 13:581–590. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Fujita E, Kouroku Y, Isoai A, Kumagai H, Misutani A, Matsuda C, Hayashi YK and Momoi T: Two endoplasmic reticulum-associated degradation (ERAD) systems for the novel variant of the mutant dysferlin: Ubiquitin/proteasome ERAD(I) and autophagy/lysosome ERAD(II). Hum Mol Genet. 16:618–629. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Yorimitsu T, Nair U, Yang Z and Klionsky DJ: Endoplasmic reticulum stress triggers autophagy. J Biol Chem. 281:30299–30304. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Gavilán MP, Pintado C, Gavilán E, Jiménez S, Ríos RM, Vitorica J, Castaño A and Ruano D: Dysfunction of the unfolded protein response increases neurodegeneration in aged rat hippo-campus following proteasome inhibition. Aging Cell. 8:654–665. 2009. View Article : Google Scholar

25 

Younce CW and Kolattukudy PE: MCP-1 causes cardiomyoblast death via autophagy resulting from ER stress caused by oxidative stress generated by inducing a novel zinc-finger protein, MCPIP. Biochem J. 426:43–53. 2010. View Article : Google Scholar

26 

Zhou F, van Laar T, Huang H and Zhang L: APP and APLP1 are degraded through autophagy in response to proteasome inhibition in neuronal cells. Protein Cell. 2:377–383. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Tanida I, Ueno T and Kominami E: LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 36:2503–2318. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Heath-Engel HM, Chang NC and Shore GC: The endoplasmic reticulum in apoptosis and autophagy: Role of the BCL-2 protein family. Oncogene. 27:6419–6433. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Oyadomari S and Mori M: Roles of CHOP/GADDI53 in endoplasmic reticulum stress. Cell Death Differ. 11:381–389. 2004. View Article : Google Scholar

30 

Yu L, Alva A, Su H, Dutt P, Freundt E, Welsh S, Baehrecke EH and Lenardo MJ: Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science. 304:1500–1502. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Cuervo AM, Stefanis L, Fredenburg R, Lansbury PT and Sulzer D: Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science. 305:1292–1295. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Rubinsztein DC, DiFiglia M, Heintz N, Dutt P, Freundt E, Welsh S, Baehrecke EH and Lenardo MJ: Autophagy and its possible roles in nervous system diseases, damage and repair. Autophagy. 1:11–22. 2005. View Article : Google Scholar

33 

Li J, Hou N, Faried A, Tsutsumi S, Takeuchi T and Kuwano H: Inhibition of autophagy by 3-MA enhances the effect of 5-FU-induced apoptosis in colon cancer cells. Ann Surg Oncol. 16:761–771. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Huang S and Sinicrope FA: Celecoxib-induced apoptosis is enhanced by ABT-737 and by inhibition of autophagy in human colorectal cancer cells. Autophagy. 6:256–269. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Walls KC, Ghosh AP, Franklin AV, Klocke BJ, Ballestas M, Shacka JJ, Zhang J and Roth KA: Lysosome dysfunction triggers Atg7-dependent neural apoptosis. J Biol Chem. 285:10497–10507. 2010. View Article : Google Scholar : PubMed/NCBI

36 

McMillan DR, Gething MJ and Sambrook J: The cellular response to unfolded proteins: Intercompartmental signaling. Curr Opin Biotechnol. 5:540–545. 1994. View Article : Google Scholar : PubMed/NCBI

37 

Gao B, Zhang XY, Han R, Zhang TT, Chen C, Qin ZH and Sheng R: The endoplasmic reticulum stress inhibitor salubrinal inhibits the activation of autophagy and neuroprotection induced by brain ischemic preconditioning. Acta Pharmacol Sin. 34:657–666. 2013. View Article : Google Scholar : PubMed/NCBI

38 

Hoyer-Hansen M and Jäättelä M: Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ. 14:1576–1582. 2007. View Article : Google Scholar : PubMed/NCBI

39 

Ding WX, Ni HM, Gao W, Yoshimori T, Stolz DB, Ron D and Yin XM: Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am J Pathol. 171:513–524. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Bao W, Gu Y, Ta L, Wang K and Xu Z: Induction of autophagy by the MG‑132 proteasome inhibitor is associated with endoplasmic reticulum stress in MCF‑7 cells. Mol Med Rep 13: 796-804, 2016.
APA
Bao, W., Gu, Y., Ta, L., Wang, K., & Xu, Z. (2016). Induction of autophagy by the MG‑132 proteasome inhibitor is associated with endoplasmic reticulum stress in MCF‑7 cells. Molecular Medicine Reports, 13, 796-804. https://doi.org/10.3892/mmr.2015.4599
MLA
Bao, W., Gu, Y., Ta, L., Wang, K., Xu, Z."Induction of autophagy by the MG‑132 proteasome inhibitor is associated with endoplasmic reticulum stress in MCF‑7 cells". Molecular Medicine Reports 13.1 (2016): 796-804.
Chicago
Bao, W., Gu, Y., Ta, L., Wang, K., Xu, Z."Induction of autophagy by the MG‑132 proteasome inhibitor is associated with endoplasmic reticulum stress in MCF‑7 cells". Molecular Medicine Reports 13, no. 1 (2016): 796-804. https://doi.org/10.3892/mmr.2015.4599
Copy and paste a formatted citation
x
Spandidos Publications style
Bao W, Gu Y, Ta L, Wang K and Xu Z: Induction of autophagy by the MG‑132 proteasome inhibitor is associated with endoplasmic reticulum stress in MCF‑7 cells. Mol Med Rep 13: 796-804, 2016.
APA
Bao, W., Gu, Y., Ta, L., Wang, K., & Xu, Z. (2016). Induction of autophagy by the MG‑132 proteasome inhibitor is associated with endoplasmic reticulum stress in MCF‑7 cells. Molecular Medicine Reports, 13, 796-804. https://doi.org/10.3892/mmr.2015.4599
MLA
Bao, W., Gu, Y., Ta, L., Wang, K., Xu, Z."Induction of autophagy by the MG‑132 proteasome inhibitor is associated with endoplasmic reticulum stress in MCF‑7 cells". Molecular Medicine Reports 13.1 (2016): 796-804.
Chicago
Bao, W., Gu, Y., Ta, L., Wang, K., Xu, Z."Induction of autophagy by the MG‑132 proteasome inhibitor is associated with endoplasmic reticulum stress in MCF‑7 cells". Molecular Medicine Reports 13, no. 1 (2016): 796-804. https://doi.org/10.3892/mmr.2015.4599
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