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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
August-2015 Volume 10 Issue 2

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
August-2015 Volume 10 Issue 2

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

S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin

  • Authors:
    • Jin‑Ah Park
    • Hyeon‑Ok Jin
    • Ha‑Na Lee
    • Jin‑Hee Kim
    • In‑Chul Park
    • Woo Chul Noh
    • Yoon Hwan Chang
    • Young Jun Hong
    • Keun‑Chul Kim
    • Jin Kyung Lee

  • View Affiliations / Copyright

    Affiliations: KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea, Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea, Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea , Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea , Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 200‑701, Republic of Korea
  • Pages: 829-834
    |
    Published online on: June 11, 2015
       https://doi.org/10.3892/ol.2015.3369
  • 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

Breast cancer cells possess a deregulated apoptotic pathway with increased expression levels of anti‑apoptotic B‑cell lymphoma‑2 (Bcl‑2) family proteins and ribosomal S6 kinase 1 (S6K1) protein activity. Therefore, combined interference of anti‑apoptotic Bcl‑2 family and S6K1 protein expression may be a reasonable therapeutic strategy for the treatment of patients with breast cancer. In the present study, it was identified that the administration of a combination of ABT263 [navitoclax; a Bcl‑2/Bcl‑extra large (Bcl‑xL) inhibitor] and PF4708671 (an S6K1 inhibitor) markedly increased apoptotic cell death in the BT474 breast cancer cells compared with the administration of either agent alone. Furthermore, the downregulation of Bcl‑2/Bcl‑xL and S6K1 with small interfering RNA induced a significant increase in cell death compared with RNA interference of either agent alone. Notably, combination treatment with ABT263 and PF4708671 decreased the expression level of survivin protein, with this ectopic expression of survivin attenuating cell death. Thus, the present study determined that the combined inhibition of Bcl‑2/Bcl‑xL and S6K1 may be a good strategy for treating patients with breast cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Strasser A, Harris AW, Bath ML and Cory S: Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature. 348:331–333. 1990. View Article : Google Scholar : PubMed/NCBI

2 

Green DR and Reed JC: Mitochondria and apoptosis. Science. 281:1309–1312. 1998. View Article : Google Scholar : PubMed/NCBI

3 

Deng J, Carlson N, Takeyama K, Dal Cin P, Shipp M and Letai A: BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell. 12:171–185. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Gross A, McDonnell JM and Korsmeyer SJ: BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13:1899–1911. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Callagy GM, Pharoah PD, Pinder SE, et al: Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index. Clin Cancer Res. 12:2468–2475. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Dawson SJ, Makretsov N, Blows FM, et al: BCL2 in breast cancer: A favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received. Br J Cancer. 103:668–675. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Tse C, Shoemaker AR, Adickes J, et al: ABT-263: A potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 68:3421–3428. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Rudin CM, Hann CL, Garon EB, et al: Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin Cancer Res. 18:3163–3169. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Kamal A, Faazil S and Malik MS: Apoptosis-inducing agents: A patent review (2010–2013). Expert Opin Ther Pat. 24:339–354. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Hong SE, Kim EK, Jin HO, et al: S6K1 inhibition enhances tamoxifen-induced cell death in MCF-7 cells through translational inhibition of Mcl-1 and survivin. Cell Biol Toxicology. 29:273–282. 2013. View Article : Google Scholar

11 

Bärlund M, Forozan F, Kononen J, et al: Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis. J Natl Cancer Inst. 92:1252–1259. 2000. View Article : Google Scholar : PubMed/NCBI

12 

Brugge J, Hung MC and Mills GB: A new mutational AKTivation in the PI3K pathway. Cancer Cell. 12:104–107. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Sinclair CS, Rowley M, Naderi A and Couch FJ: The 17q23 amplicon and breast cancer. Cancer Res Treat. 78:313–322. 2003. View Article : Google Scholar

14 

Kim EK, Kim JH, Kim HA, et al: Phosphorylated S6 kinase-1: A breast cancer marker predicting resistance to neoadjuvant chemotherapy. Anticancer Res. 33:4073–4079. 2013.PubMed/NCBI

15 

Jin HO, Yoon SI, Seo SK, et al: Synergistic induction of apoptosis by sulindac and arsenic trioxide in human lung cancer A549 cells via reactive oxygen species-dependent down-regulation of survivin. Biochem Pharmacol. 72:1228–1236. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Lu TS, Yiao SY, Lim K, et al: Interpretation of biological and mechanical variations between the Lowry versus Bradford method for protein quantification. N Am J Med Sci. 2:325–328. 2010.PubMed/NCBI

17 

Jin HO, Lee YH, Kim HA, et al: Inhibition of vacuolar H+ ATPase enhances sensitivity to tamoxifen via up-regulation of CHOP in breast cancer cells. Biochem Biophys Res Commun. 437:463–468. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Noh WC, Mondesire WH, Peng J, et al: Determinants of rapamycin sensitivity in breast cancer cells. Clin Cancer Res. 10:1013–1023. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Strasser A, Cory S and Adams JM: Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases. EMBO J. 30:3667–3683. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Vaillant F, Merino D, Lee L, et al: Targeting BCL-2 with the BH3 mimetic ABT-199 in estrogen receptor-positive breast cancer. Cancer Cell. 24:120–129. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Wang B, Ni Z, Dai X, et al: The Bcl-2/xL inhibitor ABT-263 increases the stability of Mcl-1 mRNA and protein in hepatocellular carcinoma cells. Mol Cancer. 13:982014. View Article : Google Scholar : PubMed/NCBI

22 

Shoemaker AR, Mitten MJ, Adickes J, et al: Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models. Clin Cancer Res. 14:3268–3277. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Ackler S, Xiao Y, Mitten MJ, et al: ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo. Mol Cancer Ther. 7:3265–3274. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Lock R, Carol H, Houghton PJ, et al: Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr Blood Cancer. 50:1181–1189. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Kim EK, Kim HA, Koh JS, et al: Phosphorylated S6K1 is a possible marker for endocrine therapy resistance in hormone receptor-positive breast cancer. Breast Cancer Res Treat. 126:93–99. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Park JA, Jin HO, Lee HN, Kim JH, Park IC, Noh WC, Chang YH, Hong YJ, Kim KC, Lee JK, Lee JK, et al: S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin. Oncol Lett 10: 829-834, 2015.
APA
Park, J., Jin, H., Lee, H., Kim, J., Park, I., Noh, W.C. ... Lee, J.K. (2015). S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin. Oncology Letters, 10, 829-834. https://doi.org/10.3892/ol.2015.3369
MLA
Park, J., Jin, H., Lee, H., Kim, J., Park, I., Noh, W. C., Chang, Y. H., Hong, Y. J., Kim, K., Lee, J. K."S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin". Oncology Letters 10.2 (2015): 829-834.
Chicago
Park, J., Jin, H., Lee, H., Kim, J., Park, I., Noh, W. C., Chang, Y. H., Hong, Y. J., Kim, K., Lee, J. K."S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin". Oncology Letters 10, no. 2 (2015): 829-834. https://doi.org/10.3892/ol.2015.3369
Copy and paste a formatted citation
x
Spandidos Publications style
Park JA, Jin HO, Lee HN, Kim JH, Park IC, Noh WC, Chang YH, Hong YJ, Kim KC, Lee JK, Lee JK, et al: S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin. Oncol Lett 10: 829-834, 2015.
APA
Park, J., Jin, H., Lee, H., Kim, J., Park, I., Noh, W.C. ... Lee, J.K. (2015). S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin. Oncology Letters, 10, 829-834. https://doi.org/10.3892/ol.2015.3369
MLA
Park, J., Jin, H., Lee, H., Kim, J., Park, I., Noh, W. C., Chang, Y. H., Hong, Y. J., Kim, K., Lee, J. K."S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin". Oncology Letters 10.2 (2015): 829-834.
Chicago
Park, J., Jin, H., Lee, H., Kim, J., Park, I., Noh, W. C., Chang, Y. H., Hong, Y. J., Kim, K., Lee, J. K."S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin". Oncology Letters 10, no. 2 (2015): 829-834. https://doi.org/10.3892/ol.2015.3369
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