• Skip to primary navigation
  • Skip to main content
SRI logo
  • About
    • Press room
    • Our history
  • Expertise
    • Advanced imaging systems
    • Artificial intelligence
    • Biomedical R&D services
    • Biomedical sciences
    • Computer vision
    • Cyber & formal methods
    • Education and learning
    • Innovation strategy and policy
    • National security
    • Ocean & space
    • Quantum
    • Robotics, sensors & devices
    • Speech & natural language
    • Video test & measurement
  • Ventures
  • NSIC
  • Careers
  • Contact
  • 日本支社
Search
Close
Biomedical sciences publications July 1, 2009

A Novel Peroxisome Proliferator-Activated Receptor Delta Antagonist, SR13904, has Anti-Proliferative Activity in Human Cancer Cells

Citation

Copy to clipboard


Zaveri, N. T., Sato, B. G., Jiang, F., Calaoagan, J., Laderoute, K., & Murphy, B. J. (2009). A novel peroxisome proliferator-activated receptor delta antagonist, SR13904, has anti-proliferative activity in human cancer cells. Cancer biology & therapy, 8(13), 1252-1261.

Abstract

The peroxisome proliferator-activated receptor delta (PPARδ) is a ligand-activated, nuclear receptor transcription factor that has a documented role in glucose and lipid homeostasis. Recent studies have implicated this nuclear receptor in numerous aspects of oncogenesis. We report herein the characterization of a novel small-molecule (SR13904) that inhibits PPARδ agonist-induced transactivation and functions as a PPARδ antagonist. SR13904 also antagonizes PPARγ transactivation, albeit with much weaker potency. SR13904 displays inhibitory effects on cellular proliferation and survival in several human carcinoma lines, including lung, breast and liver. These inhibitory effects of SR13904 on tumor cells were linked to a G1/S cell cycle block and increased apoptosis. Molecular studies show that SR13904 treatment of a lung cancer cell line, A549, results in markedly reduced levels of a number of cell cycle proteins including cyclin A and D, and cyclin dependent kinase (CDK) 2 and 4. The inhibitory effects on CDK2 appear to be transcriptional. Several of these cell cycle-related genes are known to be upregulated by PPARδ. The antitumor activities of SR13904 suggest that antagonism of PPARδ-mediated transactivation may inhibit tumorigenesis and that pharmacological inhibition of PPARδ may be a potential strategy for treatment or prevention of cancer.

↓ View online

Share this

How can we help?

Once you hit send…

We’ll match your inquiry to the person who can best help you.

Expect a response within 48 hours.

Career call to action image

Make your own mark.

Search jobs

Our work

Case studies

Publications

Timeline of innovation

Areas of expertise

Institute

Leadership

Press room

Media inquiries

Compliance

Careers

Job listings

Contact

SRI Ventures

Our locations

Headquarters

333 Ravenswood Ave
Menlo Park, CA 94025 USA

+1 (650) 859-2000

Subscribe to our newsletter


日本支社
SRI International
  • Contact us
  • Privacy Policy
  • Cookies
  • DMCA
  • Copyright © 2023 SRI International
Manage Cookie Consent
To provide the best experiences, we use technologies like cookies to store and/or access device information. Consenting to these technologies will allow us to process data such as browsing behavior or unique IDs on this site. Not consenting or withdrawing consent, may adversely affect certain features and functions.
Functional Always active
The technical storage or access is strictly necessary for the legitimate purpose of enabling the use of a specific service explicitly requested by the subscriber or user, or for the sole purpose of carrying out the transmission of a communication over an electronic communications network.
Preferences
The technical storage or access is necessary for the legitimate purpose of storing preferences that are not requested by the subscriber or user.
Statistics
The technical storage or access that is used exclusively for statistical purposes. The technical storage or access that is used exclusively for anonymous statistical purposes. Without a subpoena, voluntary compliance on the part of your Internet Service Provider, or additional records from a third party, information stored or retrieved for this purpose alone cannot usually be used to identify you.
Marketing
The technical storage or access is required to create user profiles to send advertising, or to track the user on a website or across several websites for similar marketing purposes.
Manage options Manage services Manage vendors Read more about these purposes
View preferences
{title} {title} {title}