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
May-2014 Volume 9 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
May-2014 Volume 9 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

Autophagy prevents doxorubicin‑induced apoptosis in osteosarcoma

  • Authors:
    • Dongxu Zhao
    • Hongping Yuan
    • Fei Yi
    • Chunyang Meng
    • Qingsan Zhu
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, The First Bethune Hospital, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Nephrology, The Fourth Bethune Hospital, Jilin University, Changchun, Jilin 130021, P.R. China
  • Pages: 1975-1981
    |
    Published online on: March 14, 2014
       https://doi.org/10.3892/mmr.2014.2055
  • 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

Autophagy is a process of selective degradation of cellular components. Autophagy is an adaptive process in the majority of tumor cells; it provides sufficient nutrients by degrading cellular components to enhance the survival of tumors. Osteosarcoma is the most common type of primary malignant bone tumor in children and adolescents. Identification of an improved therapeutic strategy for the treatment of osteosarcoma is urgently required. Osteosarcoma has been primarily treated by chemotherapy and the phenomena of resistance to the therapy has become increasingly common. Doxorubicin (Dox) is a classic chemotherapeutic drug for the treatment of osteosarcoma, and certain studies have suggested that Dox induces autophagy. On the basis of the protective effect of autophagy for tumors, the present study investigated whether U2OS and Saos‑2 osteosarcoma cells activate autophagy to reduce Dox‑induced apoptosis. Dox was observed to inhibit the growth of U2OS and Saos‑2 osteosarcoma cells in a concentration‑dependent manner. The results of the western blot analysis demonstrated that Dox induced increased expression levels of the apoptosis‑related proteins cleaved caspase‑3 and cytochrome c and loss of mitochondrial membrane potential (MMP) in the U2OS and Saos‑2 osteosarcoma cells. Furthermore, the results of the western blot analysis also revealed that Dox increased the expression levels of the autophagy‑related protein microtubule‑associated protein 1 light chain 3 and reduced those of p62 in the U2OS and Saos‑2 osteosarcoma cells. In order to determine the effect of autophagy on the apoptosis induced by Dox in the U2OS and Saos‑2 osteosarcoma cells, autophagy‑related protein (Atg)7 small interfering (si) RNA or the autophagy inhibitor 3‑methyladenine (3‑MA) alone or combined with Dox was used in U2OS and Saos‑2 osteosarcoma cells. The results identified that Atg7 siRNA and the autophagy inhibitor 3‑MA significantly elevated the levels of growth inhibition by Dox and markedly increased the expression levels of the apoptosis‑related proteins cleaved caspase‑3 and cytochrome c, and reduced the levels of MMP in the U2OS and Saos‑2 osteosarcoma cells, which were treated with Dox. These results indicated that autophagy was the protective mechanism used by U2OS and Saos‑2 osteosarcoma against Dox‑induced apoptosis. The inhibition of autophagy notably increases the levels of apoptosis induced by Dox. This suggested that Dox used in combination with autophagy inhibitors may effectively treat osteosarcoma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Chou AJ, Merola PR, Wexler LH, et al: Treatment of osteosarcoma at first recurrence after contemporary therapy: the Memorial Sloan-Kettering Cancer Center experience. Cancer. 104:2214–2221. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Nakase M, Inui M, Okumura K, Kamei T, Nakamura S and Tagawa T: p53 gene therapy of human osteosarcoma using a transferrin-modified cationic liposome. Mol Cancer Ther. 4:625–631. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Janeway KA and Grier HE: Sequelae of osteosarcoma medical therapy: a review of rare acute toxicities and late effects. Lancet Oncol. 11:670–678. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Yang Z and Klionsky DJ: Eaten alive: a history of macroautophagy. Nat Cell Biol. 12:814–822. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Klionsky DJ: The molecular machinery of autophagy: unanswered questions. J Cell Sci. 118:7–18. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Levine B and Klionsky DJ: Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 6:463–477. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Mizushima N: The pleiotropic role of autophagy: from protein metabolism to bactericide. Cell Death Differ. 12(Suppl 2): 1535–1541. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Rubinsztein DC, Gestwicki JE, Murphy LO and Klionsky DJ: Potential therapeutic applications of autophagy. Nat Rev Drug Discov. 6:304–312. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Huang WP and Klionsky DJ: Autophagy in yeast: a review of the molecular machinery. Cell Struct Funct. 27:409–420. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Luo S and Rubinsztein DC: Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect rescued by Bcl-xL. Cell Death Differ. 17:268–277. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Del Bello B, Toscano M, Moretti D and Maellaro E: Cisplatin-induced apoptosis inhibits autophagy, which acts as a pro-survival mechanism in human melanoma cells. PLoS One. 8:e572362013.PubMed/NCBI

12 

Hippert MM, O’Toole PS and Thorburn A: Autophagy in cancer: good, bad, or both? Cancer Res. 66:9349–9351. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Thorburn A: Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis. 13:1–9. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Djavaheri-Mergny M, Maiuri MC and Kroemer G: Cross talk between apoptosis and autophagy by caspase-mediated cleavage of Beclin 1. Oncogene. 29:1717–1719. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Hou W, Han J, Lu C, Goldstein LA and Rabinowich H: Autophagic degradation of active caspase-8: a crosstalk mechanism between autophagy and apoptosis. Autophagy. 6:891–900. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Lowe SW, Ruley HE, Jacks T and Housman DE: p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell. 74:957–967. 1993. View Article : Google Scholar : PubMed/NCBI

17 

Yu R, Shtil AA, Tan TH, Roninson IB and Kong AN: Adriamycin activates c-jun N-terminal kinase in human leukemia cells: a relevance to apoptosis. Cancer Lett. 107:73–81. 1996. View Article : Google Scholar : PubMed/NCBI

18 

Spina A, Sorvillo L, Di Maiolo F, et al: Inorganic phosphate enhances sensitivity of human osteosarcoma U2OS cells to doxorubicin via a p53-dependent pathway. J Cell Physiol. 228:198–206. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Gill J, Ahluwalia MK, Geller D and Gorlick R: New targets and approaches in osteosarcoma. Pharmacol Ther. 137:89–99. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Radetzki S, Köhne CH, von Haefen C, et al: The apoptosis promoting Bcl-2 homologues Bak and Nbk/Bik overcome drug resistance in Mdr-1-negative and Mdr-1-overexpressing breast cancer cell lines. Oncogene. 21:227–238. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Tarquini F, Tiribuzi R, Crispoltoni L, et al: Caspase 3 activation and PARP cleavage in lymphocytes from newborn babies of diabetic mothers with unbalanced glycaemic control. Cell Biochem Funct. 32:87–95. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Fong MY, Jin S, Rane M, Singh RK, Gupta R and Kakar SS: Withaferin A synergizes the therapeutic effect of doxorubicin through ROS-mediated autophagy in ovarian cancer. PLoS One. 7:e422652012. View Article : Google Scholar : PubMed/NCBI

23 

Li H, Jin X, Zhang Z, Xing Y and Kong X: Inhibition of autophagy enhances apoptosis induced by the PI3K/AKT/mTor inhibitor NVP-BEZ235 in renal cell carcinoma cells. Cell Biochem Funct. 31:427–433. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Kabeya Y, Mizushima N, Ueno T, et al: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19:5720–5728. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Kang R, Zeh HJ, Lotze MT and Tang D: The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ. 18:571–580. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Zhong JT, Xu Y, Yi HW, et al: The BH3 mimetic S1 induces autophagy through ER stress and disruption of Bcl-2/Beclin 1 interaction in human glioma U251 cells. Cancer Lett. 323:180–187. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Chang Z, Shi G, Jin J, et al: Dual PI3K/mTOR inhibitor NVP-BEZ235-induced apoptosis of hepatocellular carcinoma cell lines is enhanced by inhibitors of autophagy. Int J Mol Med. 31:1449–1456. 2013.PubMed/NCBI

28 

Fimia GM and Piacentini M: Regulation of autophagy in mammals and its interplay with apoptosis. Cell Mol Life Sci. 67:1581–1588. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhao D, Yuan H, Yi F, Meng C and Zhu Q: Autophagy prevents doxorubicin‑induced apoptosis in osteosarcoma. Mol Med Rep 9: 1975-1981, 2014.
APA
Zhao, D., Yuan, H., Yi, F., Meng, C., & Zhu, Q. (2014). Autophagy prevents doxorubicin‑induced apoptosis in osteosarcoma. Molecular Medicine Reports, 9, 1975-1981. https://doi.org/10.3892/mmr.2014.2055
MLA
Zhao, D., Yuan, H., Yi, F., Meng, C., Zhu, Q."Autophagy prevents doxorubicin‑induced apoptosis in osteosarcoma". Molecular Medicine Reports 9.5 (2014): 1975-1981.
Chicago
Zhao, D., Yuan, H., Yi, F., Meng, C., Zhu, Q."Autophagy prevents doxorubicin‑induced apoptosis in osteosarcoma". Molecular Medicine Reports 9, no. 5 (2014): 1975-1981. https://doi.org/10.3892/mmr.2014.2055
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao D, Yuan H, Yi F, Meng C and Zhu Q: Autophagy prevents doxorubicin‑induced apoptosis in osteosarcoma. Mol Med Rep 9: 1975-1981, 2014.
APA
Zhao, D., Yuan, H., Yi, F., Meng, C., & Zhu, Q. (2014). Autophagy prevents doxorubicin‑induced apoptosis in osteosarcoma. Molecular Medicine Reports, 9, 1975-1981. https://doi.org/10.3892/mmr.2014.2055
MLA
Zhao, D., Yuan, H., Yi, F., Meng, C., Zhu, Q."Autophagy prevents doxorubicin‑induced apoptosis in osteosarcoma". Molecular Medicine Reports 9.5 (2014): 1975-1981.
Chicago
Zhao, D., Yuan, H., Yi, F., Meng, C., Zhu, Q."Autophagy prevents doxorubicin‑induced apoptosis in osteosarcoma". Molecular Medicine Reports 9, no. 5 (2014): 1975-1981. https://doi.org/10.3892/mmr.2014.2055
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