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
March-2020 Volume 43 Issue 3

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
March-2020 Volume 43 Issue 3

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

Suppression of DRP1‑mediated mitophagy increases the apoptosis of hepatocellular carcinoma cells in the setting of chemotherapy

  • Authors:
    • Min Ma
    • Xia‑Hui Lin
    • Hua‑Hua Liu
    • Rui Zhang
    • Rong‑Xin Chen
  • View Affiliations / Copyright

    Affiliations: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
  • Pages: 1010-1018
    |
    Published online on: January 22, 2020
       https://doi.org/10.3892/or.2020.7476
  • 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 efficacy of chemotherapy for hepatocellular carcinoma (HCC) remains unsatisfactory, primarily due to inherent self‑defense mechanisms (e.g., mitophagy and autophagy). In the present study, we aimed to explore the pro‑apoptotic effects of targeting mitophagy to potentiate the efficacy of chemotherapy for HCC. HCC cells were subjected to cisplatin, after which cisplatin‑induced mitophagy was quantified by immunofluorescence. Mdivi‑1, a specific dynamin‑related protein 1 (DRP1) inhibitor, was used to study the role of DRP1 in cisplatin‑induced HCC mitophagy. The synergistic effect of cisplatin and the DRP1 inhibitor on HCC was assessed in vitro and in vivo. Accordingly, cisplatin induced mitophagy in surviving HCC cells by activating DRP1. The DRP1 inhibitor (Mdivi‑1) increased the apoptosis of cisplatin‑treated HCC cells by targeting mitophagy. Mechanistically, Mdivi‑1 upregulated Bax and downregulated Bcl‑xL, leading to an increase in mitochondrial membrane permeability and subsequent release of cytochrome c from mitochondria into the cytosol, thereby aggravating cisplatin‑induced apoptosis in HCC cells. Moreover, Mdivi‑1 acted synergistically with cisplatin to suppress HCC xenograft growth in vivo. Our results indicate that targeting cisplatin‑mediated mitophagy increases HCC apoptosis via DRP1 inhibition, providing preclinical proof of concept for combination therapy targeting mitophagy to potentiate the efficacy of chemotherapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

European Association for the Study of the Liver. Electronic address, . simpleeasloffice@easloffice.eu; European Association for the Study of the Liver: EASL clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol. 69:182–236. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Nowak AK, Chow PK and Findlay M: Systemic therapy for advanced hepatocellular carcinoma: A review. Eur J Cancer. 40:1474–1484. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Qin S, Bai Y, Lim HY, Thongprasert S, Chao Y, Fan J, Yang TS, Bhudhisawasdi V, Kang WK, Zhou Y, et al: Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 31:3501–3508. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Li J, Duan B, Guo Y, Zhou R, Sun J, Bie B, Yang S, Huang C, Yang J and Li Z: Baicalein sensitizes hepatocellular carcinoma cells to 5-FU and epirubicin by activating apoptosis and ameliorating P-glycoprotein activity. Biomed Pharmacother. 98:806–812. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Lee TK, Castilho A, Cheung VC, Tang KH, Ma S and Ng IO: CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation. Cell Stem Cell. 9:50–63. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Roos WP, Thomas AD and Kaina B: DNA damage and the balance between survival and death in cancer biology. Nat Rev Cancer. 16:20–33. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Lo SJ, Fan LC, Tsai YF, Lin KY, Huang HL, Wang TH, Liu H, Chen TC, Huang SF, Chang CJ, et al: A novel interaction of nucleophosmin with BCL2-associated X protein regulating death evasion and drug sensitivity in human hepatoma cells. Hepatology. 57:1893–1905. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Ding ZB, Hui B, Shi YH, Zhou J, Peng YF, Gu CY, Yang H, Shi GM, Ke AW, Wang XY, et al: Autophagy activation in hepatocellular carcinoma contributes to the tolerance of oxaliplatin via reactive oxygen species modulation. Clin Cancer Res. 17:6229–6238. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Ashrafi G and Schwarz TL: The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ. 20:31–42. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Vives-Bauza C, Zhou C, Huang Y, Cui M, de Vries RL, Kim J, May J, Tocilescu MA, Liu W, Ko HS, et al: PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA. 107:378–383. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Youle RJ and Narendra DP: Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 12:9–14. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Eisner V, Picard M and Hajnóczky G: Mitochondrial dynamics in adaptive and maladaptive cellular stress responses. Nat Cell Biol. 20:755–765. 2018. View Article : Google Scholar : PubMed/NCBI

13 

Roy M, Reddy PH, Iijima M and Sesaki H: Mitochondrial division and fusion in metabolism. Curr Opin Cell Biol. 33:111–118. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Fang EF, Palikaras K, Sun N, Fivenson EM, Spangler RD, Kerr JS, Cordonnier SA, Hou Y, Dombi E, Kassahun H, et al: In vitro and in vivo detection of mitophagy in human cells, C. elegans, and mice. J Vis Exp. 22:2017.

15 

Shimizu S and Tsujimoto Y: Proapoptotic BH3-only Bcl-2 family members induce cytochrome c release, but not mitochondrial membrane potential loss, and do not directly modulate voltage-dependent anion channel activity. Proc Natl Acad Sci USA. 97:577–582. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Shimizu S, Narita M and Tsujimoto Y and Tsujimoto Y: Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature. 399:483–487. 1999. View Article : Google Scholar : PubMed/NCBI

17 

Vander Heiden MG, Chandel NS, Williamson EK, Schumacker PT and Thompson CB: Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria. Cell. 91:627–637. 1997. View Article : Google Scholar : PubMed/NCBI

18 

Kubli DA and Gustafsson AB: Mitochondria and mitophagy: The yin and yang of cell death control. Circ Res. 111:1208–1221. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Zhou H, Zhu P, Guo J, Hu N, Wang S, Li D, Hu S, Ren J, Cao F and Chen Y: Ripk3 induces mitochondrial apoptosis via inhibition of FUNDC1 mitophagy in cardiac IR injury. Redox Biol. 13:498–507. 2017. View Article : Google Scholar : PubMed/NCBI

20 

Debatin KM, Poncet D and Kroemer G: Chemotherapy: Targeting the mitochondrial cell death pathway. Oncogene. 21:8786–8803. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Graef M: A dividing matter: Drp1/Dnm1-independent mitophagy. J Cell Biol. 215:599–601. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Lima AR, Santos L, Correia M, Soares P, Sobrinho-Simões M, Melo M and Máximo V: Dynamin-related protein 1 at the crossroads of cancer. Genes (Basel). 9:E1152018. View Article : Google Scholar : PubMed/NCBI

23 

Galluzzi L, Vitale I, Michels J, Brenner C, Szabadkai G, Harel-Bellan A, Castedo M and Kroemer G: Systems biology of cisplatin resistance: Past, present and future. Cell Death Dis. 5:e12572014. View Article : Google Scholar : PubMed/NCBI

24 

Marullo R, Werner E, Degtyareva N, Moore B, Altavilla G, Ramalingam SS and Doetsch PW: Cisplatin induces a mitochondrial-ROS response that contributes to cytotoxicity depending on mitochondrial redox status and bioenergetic functions. PLoS One. 8:e811622013. View Article : Google Scholar : PubMed/NCBI

25 

Cassidy-Stone A, Chipuk JE, Ingerman E, Song C, Yoo C, Kuwana T, Kurth MJ, Shaw JT, Hinshaw JE, Green DR and Nunnari J: Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell. 14:193–204. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Li H, Alavian KN, Lazrove E, Mehta N, Jones A, Zhang P, Licznerski P, Graham M, Uo T, Guo J, et al: A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis. Nat Cell Biol. 15:773–785. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Li H, Chen Y, Jones AF, Sanger RH, Collis LP, Flannery R, McNay EC, Yu T, Schwarzenbacher R, Bossy B, et al: Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons. Proc Natl Acad Sci USA. 105:2169–2174. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Bordt EA, Clerc P, Roelofs BA, Saladino AJ, Tretter L, Adam-Vizi V, Cherok E, Khalil A, Yadava N, Ge SX, et al: The putative Drp1 inhibitor mdivi-1 is a reversible mitochondrial complex I inhibitor that modulates reactive oxygen species. Dev Cell. 40:583–594.e6. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ma M, Lin XH, Liu HH, Zhang R and Chen RX: Suppression of DRP1‑mediated mitophagy increases the apoptosis of hepatocellular carcinoma cells in the setting of chemotherapy. Oncol Rep 43: 1010-1018, 2020.
APA
Ma, M., Lin, X., Liu, H., Zhang, R., & Chen, R. (2020). Suppression of DRP1‑mediated mitophagy increases the apoptosis of hepatocellular carcinoma cells in the setting of chemotherapy. Oncology Reports, 43, 1010-1018. https://doi.org/10.3892/or.2020.7476
MLA
Ma, M., Lin, X., Liu, H., Zhang, R., Chen, R."Suppression of DRP1‑mediated mitophagy increases the apoptosis of hepatocellular carcinoma cells in the setting of chemotherapy". Oncology Reports 43.3 (2020): 1010-1018.
Chicago
Ma, M., Lin, X., Liu, H., Zhang, R., Chen, R."Suppression of DRP1‑mediated mitophagy increases the apoptosis of hepatocellular carcinoma cells in the setting of chemotherapy". Oncology Reports 43, no. 3 (2020): 1010-1018. https://doi.org/10.3892/or.2020.7476
Copy and paste a formatted citation
x
Spandidos Publications style
Ma M, Lin XH, Liu HH, Zhang R and Chen RX: Suppression of DRP1‑mediated mitophagy increases the apoptosis of hepatocellular carcinoma cells in the setting of chemotherapy. Oncol Rep 43: 1010-1018, 2020.
APA
Ma, M., Lin, X., Liu, H., Zhang, R., & Chen, R. (2020). Suppression of DRP1‑mediated mitophagy increases the apoptosis of hepatocellular carcinoma cells in the setting of chemotherapy. Oncology Reports, 43, 1010-1018. https://doi.org/10.3892/or.2020.7476
MLA
Ma, M., Lin, X., Liu, H., Zhang, R., Chen, R."Suppression of DRP1‑mediated mitophagy increases the apoptosis of hepatocellular carcinoma cells in the setting of chemotherapy". Oncology Reports 43.3 (2020): 1010-1018.
Chicago
Ma, M., Lin, X., Liu, H., Zhang, R., Chen, R."Suppression of DRP1‑mediated mitophagy increases the apoptosis of hepatocellular carcinoma cells in the setting of chemotherapy". Oncology Reports 43, no. 3 (2020): 1010-1018. https://doi.org/10.3892/or.2020.7476
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