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
March-2018 Volume 15 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-2018 Volume 15 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

Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines

  • Authors:
    • Roman C. Brands
    • Mario J.J. Scheurer
    • Stefan Hartmann
    • Axel Seher
    • Alexander C. Kübler
    • Urs D.A. Müller‑Richter
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D‑97070 Würzburg, Germany
  • Pages: 4010-4016
    |
    Published online on: January 12, 2018
       https://doi.org/10.3892/ol.2018.7783
  • 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

Inhibitor of apoptosis proteins, which are overexpressed in head and neck squamous cell carcinoma (HNSCC), may cause therapeutic resistance. Using SMAC mimetic compounds, including birinapant, to degrade and/or inhibit these proteins and sensitize apoptosis may enhance therapies in HNSCC. Fas expression was analyzed in nine HNSCC cell lines and one keratinocyte cell line via flow cytometry. These cell lines were treated with Fas ligand‑Fc (FasL) and birinapant, a bivalent SMAC mimetic, in mono and combination therapies. Cytotoxicity was measured using a crystal violet assay. Annexin V assay was performed for detection of apoptosis. The treatment efficacy of mono and combination therapies was statistically analyzed. Nonlinear regression analysis was performed to determine the inhibitory concentration (IC10) of birinapant. Fas expression was detected in each cell line tested. Mono treatment with FasL revealed minor to no apoptotic effects in the majority of the cell lines. Crystal violet and Annexin V staining revealed increased apoptosis rates for all cell lines following incubation with birinapant in mono treatment. Combination treatment with FasL and birinapant (IC10) revealed additional and synergistic effects in eight out of the ten cell lines. To the best of our knowledge, the present study provided the first evidence of the apoptosis‑sensitizing activity of combination treatment with FasL and birinapant in HNSCC cell lines.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Kamangar F, Dores GM and Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 24:2137–2150. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Gupta S, Kong W, Peng Y, Miao Q and Mackillop WJ: Temporal trends in the incidence and survival of cancers of the upper aerodigestive tract in Ontario and the United States. Int J Cancer. 125:2159–2165. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Moreira J, Tobias A, O'Brien MP and Agulnik M: Targeted therapy in head and neck cancer: An update on current clinical developments in epidermal growth factor receptor-targeted therapy and immunotherapies. Drugs. 77:843–857. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2017. View Article : Google Scholar

6 

Fulda S: Promises and challenges of smac mimetics as cancer therapeutics. Clin Cancer Res. 21:5030–5036. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Derakhshan A, Chen Z and Van Waes C: Therapeutic small molecules target inhibitor of apoptosis proteins in cancers with deregulation of extrinsic and intrinsic cell death pathways. Clin Cancer Res. 23:1379–1387. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Johnstone RW, Ruefli AA and Lowe SW: Apoptosis: A link between cancer genetics and chemotherapy. Cell. 108:153–164. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Yu J and Zhang L: Apoptosis in human cancer cells. Curr Opin Oncol. 16:19–24. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Sun Q, Zheng X, Zhang L and Yu J: Smac modulates chemosensitivity in head and neck cancer cells through the mitochondrial apoptotic pathway. Clin Cancer Res. 17:2361–2372. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Yang XH, Feng ZE, Yan M, Hanada S, Zuo H, Yang CZ, Han ZG, Guo W, Chen WT and Zhang P: XIAP is a predictor of cisplatin-based chemotherapy response and prognosis for patients with advanced head and neck cancer. PLoS One. 7:e316012012. View Article : Google Scholar : PubMed/NCBI

12 

Matzinger O, Viertl D, Tsoutsou P, Kadi L, Rigotti S, Zanna C, Wiedemann N, Vozenin MC, Vuagniaux G and Bourhis J: The radiosensitizing activity of the SMAC-mimetic, Debio 1143, is TNFα-mediated in head and neck squamous cell carcinoma. Radiother Oncol. 116:495–503. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Eytan DF, Snow GE, Carlson SG, Schiltz S, Chen Z and Van Waes C: Combination effects of SMAC mimetic birinapant with TNFα, TRAIL, and docetaxel in preclinical models of HNSCC. Laryngoscope. 125:E118–E124. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Medicine USNLo: ClinicalTrials.gov, . U.S. National Library of Medicine. Rockville Pike, Bethesda: 2017, https://clinicaltrials.gov/ct2/results?cond=solid&term=smac&cntry1=&state1=&Search=SearchAugust 7–2017

15 

Brands RC, Herbst F, Hartmann S, Seher A, Linz C, Kübler AC and Müller-Richter UDA: Cytotoxic effects of SMAC-mimetic compound LCL161 in head and neck cancer cell lines. Clin Oral Investig. 20:2325–2332. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Brands RC, Muller-Richter UD, De Donno F, Seher A, Mutzbauer G, Linz C, Kübler AC and Hartmann S: Co-treatment of wild-type EGFR head and neck cancer cell lines with afatinib and cisplatin. Mol Med Rep. 13:2338–2344. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Eytan DF, Snow GE, Carlson S, Derakhshan A, Saleh A, Schiltz S, Cheng H, Mohan S, Cornelius S, Coupar J, et al: SMAC mimetic birinapant plus radiation eradicates human head and neck cancers with genomic amplifications of cell death genes FADD and BIRC2. Cancer Res. 76:5442–5454. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE and Forastiere AA: An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 21:92–98. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Samarasinghe B: Hallmarks of Cancer 3: Evading Apoptosis. Scientific American. 2013.https://blogs.scientificamerican.com/guest-blog/hallmarks-of-cancer-3-evading-apoptosis/August 7–2017

20 

De Maria S, Pannone G, Bufo P, Santoro A, Serpico R, Metafora S, Rubini C, Pasquali D, Papagerakis SM, Staibano S, et al: Survivin gene-expression and splicing isoforms in oral squamous cell carcinoma. J Cancer Res Clin Oncol. 135:107–116. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Khan Z and Bisen PS: Oncoapoptotic signaling and deregulated target genes in cancers: Special reference to oral cancer. Biochim Biophys Acta. 1836:123–145. 2013.PubMed/NCBI

22 

Chen DJ and Huerta S: Smac mimetics as new cancer therapeutics. Anticancer Drugs. 20:646–658. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Koff JL, Ramachandiran S and Bernal-Mizrachi L: A time to kill: Targeting apoptosis in cancer. Int J Mol Sci. 16:2942–2955. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Amaravadi RK, Schilder RJ, Martin LP, Levin M, Graham MA, Weng DE and Adjei AA: A phase I study of the SMAC-mimetic birinapant in adults with refractory solid tumors or lymphoma. Mol Cancer Ther. 14:2569–2675. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Infante JR, Dees EC, Olszanski AJ, Dhuria SV, Sen S, Cameron S and Cohen RB: Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. J Clin Oncol. 32:3103–3110. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Tolcher AW, Bendell JC, Papadopoulos KP, Burris HA, Patnaik A, Fairbrother WJ, Wong H, Budha N, Darbonne WC, Peale F, et al: A phase I dose-escalation study evaluating the safety tolerability and pharmacokinetics of CUDC-427, a potent, oral, monovalent IAP antagonist, in patients with refractory solid tumors. Clin Cancer Res. 22:4567–4573. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Khan Z, Khan N, Tiwari RP, Patro IK, Prasad GB and Bisen PS: Down-regulation of survivin by oxaliplatin diminishes radioresistance of head and neck squamous carcinoma cells. Radiother Oncol. 96:267–273. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Qi G, Kudo Y, Ando T, Tsunematsu T, Shimizu N, Siriwardena SB, Yoshida M, Keikhaee MR, Ogawa I and Takata T: Nuclear Survivin expression is correlated with malignant behaviors of head and neck cancer together with Aurora-B. Oral Oncol. 46:263–270. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Khan Z, Tiwari RP, Khan N, Prasad GB and Bisen PS: Induction of apoptosis and sensitization of head and neck squamous carcinoma cells to cisplatin by targeting survivin gene expression. Curr Gene Ther. 12:444–53. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schröter M, Burns K, Mattmann C, et al: Inhibition of death receptor signals by cellular FLIP. Nature. 388:190–195. 1997. View Article : Google Scholar : PubMed/NCBI

31 

Kataoka T, Budd RC, Holler N, Thome M, Martinon F, Irmler M, Burns K, Hahne M, Kennedy N, Kovacsovics M and Tschopp J: The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways. Curr Biol. 10:640–648. 2000. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Brands RC, Scheurer MJ, Hartmann S, Seher A, Kübler AC and Müller‑Richter UD: Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines. Oncol Lett 15: 4010-4016, 2018.
APA
Brands, R.C., Scheurer, M.J., Hartmann, S., Seher, A., Kübler, A.C., & Müller‑Richter, U.D. (2018). Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines. Oncology Letters, 15, 4010-4016. https://doi.org/10.3892/ol.2018.7783
MLA
Brands, R. C., Scheurer, M. J., Hartmann, S., Seher, A., Kübler, A. C., Müller‑Richter, U. D."Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines". Oncology Letters 15.3 (2018): 4010-4016.
Chicago
Brands, R. C., Scheurer, M. J., Hartmann, S., Seher, A., Kübler, A. C., Müller‑Richter, U. D."Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines". Oncology Letters 15, no. 3 (2018): 4010-4016. https://doi.org/10.3892/ol.2018.7783
Copy and paste a formatted citation
x
Spandidos Publications style
Brands RC, Scheurer MJ, Hartmann S, Seher A, Kübler AC and Müller‑Richter UD: Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines. Oncol Lett 15: 4010-4016, 2018.
APA
Brands, R.C., Scheurer, M.J., Hartmann, S., Seher, A., Kübler, A.C., & Müller‑Richter, U.D. (2018). Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines. Oncology Letters, 15, 4010-4016. https://doi.org/10.3892/ol.2018.7783
MLA
Brands, R. C., Scheurer, M. J., Hartmann, S., Seher, A., Kübler, A. C., Müller‑Richter, U. D."Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines". Oncology Letters 15.3 (2018): 4010-4016.
Chicago
Brands, R. C., Scheurer, M. J., Hartmann, S., Seher, A., Kübler, A. C., Müller‑Richter, U. D."Apoptosis-sensitizing activity of birinapant in head and neck squamous cell carcinoma cell lines". Oncology Letters 15, no. 3 (2018): 4010-4016. https://doi.org/10.3892/ol.2018.7783
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