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
December-2016 Volume 36 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
December-2016 Volume 36 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

Enhancement of radiosensitivity by inhibition of c-Jun N-terminal kinase activity in a Lewis lung carcinoma‑bearing subcutaneous tumor mouse model

  • Authors:
    • Chun-Hao Li
    • Sa-Hoe Lim
    • Hyang-Hwa Ryu
    • Kyung‑Sub Moon
    • Tae-Young Jung
    • Shin Jung
  • View Affiliations / Copyright

    Affiliations: Brain Tumor Research Laboratory, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do 519-763, Republic of Korea, Department of Neurosurgery, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do 519-763, Republic of Korea
  • Pages: 3397-3404
    |
    Published online on: October 25, 2016
       https://doi.org/10.3892/or.2016.5204
  • 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

Stereotactic radiosurgery has been recognized as an effective treatment approach for metastatic brain tumors. By increasing the sensitivity of the tumor to radiation and decreasing the marginal dose, it is possible to improve therapeutic efficacy and decrease side-effects. In radiation-induced cells, c-Jun N-terminal kinase (JNK) signaling mediates the phosphorylation of H2AX, which indicates DNA damage sensitivity and modulates the effect of radiation. Lewis lung cancer (LLC) and breast cancer (4T1) cells were irradiated with a Gamma Knife in cell culture tubes. To evaluate the relationship between radiosensitivity and JNK activity, clonogenic assay was performed. DNA damage response was estimated by γH2AX focus formation assay and apoptosis‑related protein levels were assessed by western blotting. The mice were subcutaneously inoculated with LLC cells, and irradiated concomitantly with JNK inhibitor treatment. The effect of the JNK inhibitor was investigated by tumor volumetry and immunohistochemistry. γH2AX expression, which mediates repair of radiation‑induced DNA damage, was reduced in the cancer cell group pretreated with the JNK inhibitor. This finding shows that JNK inhibition may increase the radiosensitivity in radiated lung and breast cancer cells. For the in vivo study, irradiated tumor growth was significantly delayed in the JNK inhibitor-treated mouse group. Blockade of JNK signaling decreased γH2AX expression and increased apoptosis in the radiation-induced cancer cells. JNK inhibitor may be useful for enhancing the radiosensitivity of lung and breast cancer cells and improving the treatment efficacy of radiosurgical approaches for metastatic brain tumors.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Davis RJ: Signal transduction by the JNK group of MAP kinases. Cell. 103:239–252. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Bode AM and Dong Z: The functional contrariety of JNK. Mol Carcinog. 46:591–598. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Weston CR and Davis RJ: The JNK signal transduction pathway. Curr Opin Cell Biol. 19:142–149. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Lu C, Zhu F, Cho YY, Tang F, Zykova T, Ma WY, Bode AM and Dong Z: Cell apoptosis: Requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3. Mol Cell. 23:121–132. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Yue WY, Clark JJ, Telisak M and Hansen MR: Inhibition of c-Jun N-terminal kinase activity enhances vestibular schwannoma cell sensitivity to gamma irradiation. Neurosurgery. 73:506–516. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Bennett BL, Sasaki DT, Murray BW, O'Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y, et al: SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci USA. 98:13681–13686. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Guan QH, Pei DS, Zhang QG, Hao ZB, Xu TL and Zhang GY: The neuroprotective action of SP600125, a new inhibitor of JNK, on transient brain ischemia/reperfusion-induced neuronal death in rat hippocampal CA1 via nuclear and non-nuclear pathways. Brain Res. 1035:51–59. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Li S, Li C, Ryu HH, Lim SH, Jang WY and Jung S: Bacitracin inhibits the migration of U87-MG glioma cells via interferences of the integrin outside-in signaling pathway. J Korean Neurosurg Soc. 59:106–116. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Jin SG, Ryu HH, Li SY, Li CH, Lim SH, Jang WY and Jung S: Nogo-A inhibits the migration and invasion of human malignant glioma U87MG cells. Oncol Rep. 35:3395–3402. 2016.PubMed/NCBI

10 

Wen M, Jung S, Moon KS, Jiang SN, Li SY and Min JJ: Targeting orthotopic glioma in mice with genetically engineered Salmonella typhimurium. J Korean Neurosurg Soc. 55:131–135. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Wang W, Shi L, Xie Y, Ma C, Li W, Su X, Huang S, Chen R, Zhu Z, Mao Z, et al: SP600125, a new JNK inhibitor, protects dopaminergic neurons in the MPTP model of Parkinson's disease. Neurosci Res. 48:195–202. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Yue WY, Clark JJ, Fernando A, Domann F and Hansen MR: Contribution of persistent C-Jun N-terminal kinase activity to the survival of human vestibular schwannoma cells by suppression of accumulation of mitochondrial superoxides. Neuro Oncol. 13:961–973. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Lin NU, Bellon JR and Winer EP: CNS metastases in breast cancer. J Clin Oncol. 22:3608–3617. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Shaw MG and Ball DL: Treatment of brain metastases in lung cancer: Strategies to avoid/reduce late complications of whole brain radiation therapy. Curr Treat Options Oncol. 14:553–567. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Jackson SP and Bartek J: The DNA-damage response in human biology and disease. Nature. 461:1071–1078. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Fernandez-Capetillo O, Chen HT, Celeste A, Ward I, Romanienko PJ, Morales JC, Naka K, Xia Z, Camerini-Otero RD, Motoyama N, et al: DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1. Nat Cell Biol. 4:993–997. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M and Bonner WM: A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol. 10:886–895. 2000. View Article : Google Scholar : PubMed/NCBI

18 

Burma S, Chen BP, Murphy M, Kurimasa A and Chen DJ: ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem. 276:42462–42467. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Wang H, Wang M, Wang H, Böcker W and Iliakis G: Complex H2AX phosphorylation patterns by multiple kinases including ATM and DNA-PK in human cells exposed to ionizing radiation and treated with kinase inhibitors. J Cell Physiol. 202:492–502. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Ward IM and Chen J: Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem. 276:47759–47762. 2001.PubMed/NCBI

21 

Hibi M, Lin A, Smeal T, Minden A and Karin M: Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 7:2135–2148. 1993. View Article : Google Scholar : PubMed/NCBI

22 

Waetzig V and Herdegen T: Context-specific inhibition of JNKs: Overcoming the dilemma of protection and damage. Trends Pharmacol Sci. 26:455–461. 2005.PubMed/NCBI

23 

Oltmanns U, Issa R, Sukkar MB, John M and Chung KF: Role of c-jun N-terminal kinase in the induced release of GM-CSF, RANTES and IL-8 from human airway smooth muscle cells. Br J Pharmacol. 139:1228–1234. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Barr RK, Kendrick TS and Bogoyevitch MA: Identification of the critical features of a small peptide inhibitor of JNK activity. J Biol Chem. 277:10987–10997. 2002. View Article : Google Scholar : PubMed/NCBI

25 

An J, Huang YC, Xu QZ, Zhou LJ, Shang ZF, Huang B, Wang Y, Liu XD, Wu DC and Zhou PK: DNA-PKcs plays a dominant role in the regulation of H2AX phosphorylation in response to DNA damage and cell cycle progression. BMC Mol Biol. 11:182010. View Article : Google Scholar : PubMed/NCBI

26 

Kim CH, Won M, Choi CH, Ahn J, Kim BK, Song KB, Kang CM and Chung KS: Increase of RhoB in gamma-radiation-induced apoptosis is regulated by c-Jun N-terminal kinase in Jurkat T cells. Biochem Biophys Res Commun. 391:1182–1186. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Han Y, Wang Y, Xu HT, Yang LH, Wei Q, Liu Y, Zhang Y, Zhao Y, Dai SD, Miao Y, et al: X-radiation induces non-small-cell lung cancer apoptosis by upregulation of Axin expression. Int J Radiat Oncol Biol Phys. 75:518–526. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Gao Z, Sarsour EH, Kalen AL, Li L, Kumar MG and Goswami PC: Late ROS accumulation and radiosensitivity in SOD1-overexpressing human glioma cells. Free Radic Biol Med. 45:1501–1509. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Shen HM and Liu ZG: JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species. Free Radic Biol Med. 40:928–939. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Jena NR: DNA damage by reactive species: Mechanisms, mutation and repair. J Biosci. 37:503–517. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Yu CC, Ko FY, Yu CS, Lin CC, Huang YP, Yang JS, Lin JP and Chung JG: Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells. Int J Oncol. 41:1050–1060. 2012.PubMed/NCBI

32 

Zeng H, Kong X, Peng H, Chen Y, Cai S, Luo H and Chen P: Apoptosis and Bcl-2 family proteins, taken to chronic obstructive pulmonary disease. Eur Rev Med Pharmacol Sci. 16:711–727. 2012.PubMed/NCBI

33 

Tang S, Hu J, Meng Q, Dong X, Wang K, Qi Y, Chu C, Zhang X and Hou L: Daidzein induced apoptosis via down-regulation of Bcl-2/Bax and triggering of the mitochondrial pathway in BGC-823 cells. Cell Biochem Biophys. 65:197–202. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Miwa M and Masutani M: PolyADP-ribosylation and cancer. Cancer Sci. 98:1528–1535. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Wei L, Nakajima S, Hsieh CL, Kanno S, Masutani M, Levine AS, Yasui A and Lan L: Damage response of XRCC1 at sites of DNA single strand breaks is regulated by phosphorylation and ubiquitylation after degradation of poly(ADP-ribose). J Cell Sci. 126:4414–4423. 2013. View Article : Google Scholar : PubMed/NCBI

36 

Germain M, Affar EB, D'Amours D, Dixit VM, Salvesen GS and Poirier GG: Cleavage of automodified poly(ADP-ribose) polymerase during apoptosis. Evidence for involvement of caspase-7. J Biol Chem. 274:28379–28384. 1999. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li C, Lim S, Ryu H, Moon KS, Jung T and Jung S: Enhancement of radiosensitivity by inhibition of c-Jun N-terminal kinase activity in a Lewis lung carcinoma‑bearing subcutaneous tumor mouse model. Oncol Rep 36: 3397-3404, 2016.
APA
Li, C., Lim, S., Ryu, H., Moon, K., Jung, T., & Jung, S. (2016). Enhancement of radiosensitivity by inhibition of c-Jun N-terminal kinase activity in a Lewis lung carcinoma‑bearing subcutaneous tumor mouse model. Oncology Reports, 36, 3397-3404. https://doi.org/10.3892/or.2016.5204
MLA
Li, C., Lim, S., Ryu, H., Moon, K., Jung, T., Jung, S."Enhancement of radiosensitivity by inhibition of c-Jun N-terminal kinase activity in a Lewis lung carcinoma‑bearing subcutaneous tumor mouse model". Oncology Reports 36.6 (2016): 3397-3404.
Chicago
Li, C., Lim, S., Ryu, H., Moon, K., Jung, T., Jung, S."Enhancement of radiosensitivity by inhibition of c-Jun N-terminal kinase activity in a Lewis lung carcinoma‑bearing subcutaneous tumor mouse model". Oncology Reports 36, no. 6 (2016): 3397-3404. https://doi.org/10.3892/or.2016.5204
Copy and paste a formatted citation
x
Spandidos Publications style
Li C, Lim S, Ryu H, Moon KS, Jung T and Jung S: Enhancement of radiosensitivity by inhibition of c-Jun N-terminal kinase activity in a Lewis lung carcinoma‑bearing subcutaneous tumor mouse model. Oncol Rep 36: 3397-3404, 2016.
APA
Li, C., Lim, S., Ryu, H., Moon, K., Jung, T., & Jung, S. (2016). Enhancement of radiosensitivity by inhibition of c-Jun N-terminal kinase activity in a Lewis lung carcinoma‑bearing subcutaneous tumor mouse model. Oncology Reports, 36, 3397-3404. https://doi.org/10.3892/or.2016.5204
MLA
Li, C., Lim, S., Ryu, H., Moon, K., Jung, T., Jung, S."Enhancement of radiosensitivity by inhibition of c-Jun N-terminal kinase activity in a Lewis lung carcinoma‑bearing subcutaneous tumor mouse model". Oncology Reports 36.6 (2016): 3397-3404.
Chicago
Li, C., Lim, S., Ryu, H., Moon, K., Jung, T., Jung, S."Enhancement of radiosensitivity by inhibition of c-Jun N-terminal kinase activity in a Lewis lung carcinoma‑bearing subcutaneous tumor mouse model". Oncology Reports 36, no. 6 (2016): 3397-3404. https://doi.org/10.3892/or.2016.5204
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