Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
OtherArticle

Senolytic-mediated elimination of head and neck tumor cells induced into senescence by cisplatin

Fereshteh Ahmadinejad, Tasia Bos, Bin Hu, Erin Britt, Jennifer Koblinski, Andrew J Souers, Joel D. Leverson, Anthony C. Faber, David A. Gewirtz and Hisashi Harada
Molecular Pharmacology December 14, 2021, MOLPHARM-AR-2021-000354; DOI: https://doi.org/10.1124/molpharm.121.000354
Fereshteh Ahmadinejad
1Human and Molecular Genetics, Virginia Commonwealth University, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tasia Bos
2Virginia Commonwealth University, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bin Hu
2Virginia Commonwealth University, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erin Britt
2Virginia Commonwealth University, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jennifer Koblinski
2Virginia Commonwealth University, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew J Souers
3Abbvie, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joel D. Leverson
4AbbVie, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anthony C. Faber
2Virginia Commonwealth University, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David A. Gewirtz
5Dept. of Medicine, Virginia Commonwealth University, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hisashi Harada
6Massey Cancer Center, VCU, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: hharada@vcu.edu
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

Abstract

Therapeutic outcomes achieved in head and neck squamous cell carcinoma (HNSCC) patients by concurrent cisplatin-based chemoradiotherapy initially reflect both tumor regression and tumor stasis. However, local and distant metastasis and disease relapse are common in HNSCC patients. In the current work, we demonstrate that cisplatin treatment induces senescence in head and neck cancer models from which tumor cells can escape both in vitro and in vivo. We further establish the effectiveness of the senolytic, ABT-263 (Navitoclax), in elimination of senescent tumor cells after cisplatin treatment. Additionally, we show that ABT-263 interferes with the interaction between BCL-XL and BAX, anti- and pro-apoptotic proteins, respectively, followed by BAX activation. Our in vivo studies also confirm senescence induction in tumor cells by cisplatin, and the promotion of apoptosis coupled with a significant decrease in tumor size after sequential treatment with ABT-263. These results support the premise that senolytic agents could be utilized to eliminate residual senescent tumor cells after chemotherapy and thereby potentially delay disease recurrence in head and neck cancer patients.

Significance Statement Disease recurrence is the most common cause of death in head and neck cancer patients. BCL-XL inhibitors such as ABT-263 (Navitoclax) have the capacity to be used in combination with cisplatin in head and neck cancer patients to eliminate senescent cells and possibly prevent disease relapse.

  • chemotherapy
  • mechanisms of cell killing/apoptosis
  • Copyright © 2020 American Society for Pharmacology and Experimental Therapeutics
Next
Back to top

In this issue

Molecular Pharmacology: 103 (6)
Molecular Pharmacology
Vol. 103, Issue 6
1 Jun 2023
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Senolytic-mediated elimination of head and neck tumor cells induced into senescence by cisplatin
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
OtherArticle

Recovery and elimination of senescent tumor cells

Fereshteh Ahmadinejad, Tasia Bos, Bin Hu, Erin Britt, Jennifer Koblinski, Andrew J Souers, Joel D. Leverson, Anthony C. Faber, David A. Gewirtz and Hisashi Harada
Molecular Pharmacology December 14, 2021, MOLPHARM-AR-2021-000354; DOI: https://doi.org/10.1124/molpharm.121.000354

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
OtherArticle

Recovery and elimination of senescent tumor cells

Fereshteh Ahmadinejad, Tasia Bos, Bin Hu, Erin Britt, Jennifer Koblinski, Andrew J Souers, Joel D. Leverson, Anthony C. Faber, David A. Gewirtz and Hisashi Harada
Molecular Pharmacology December 14, 2021, MOLPHARM-AR-2021-000354; DOI: https://doi.org/10.1124/molpharm.121.000354
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Cysteine151 in Keap1 Drives CDDO-Me Pharmacodynamic Action
  • Allosteric Modulation of Metabotropic Glutamate Receptor 1
  • Mechanism of Selective Action of Paraherquamide A
Show more Article

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics