A SIRT2-Selective Inhibitor Promotes c-Myc Oncoprotein Degradation and Exhibits Broad Anticancer Activity Academic Article uri icon

Overview

MeSH Major

  • Antineoplastic Agents
  • Oncogene Proteins
  • Proteolysis
  • Proto-Oncogene Proteins c-myc
  • Sirtuin 2

abstract

  • Targeting sirtuins for cancer treatment has been a topic of debate due to conflicting reports and lack of potent and specific inhibitors. We have developed a thiomyristoyl lysine compound, TM, as a potent SIRT2-specific inhibitor with a broad anticancer effect in various human cancer cells and mouse models of breast cancer. Mechanistically, SIRT2 inhibition promotes c-Myc ubiquitination and degradation. The anticancer effect of TM correlates with its ability to decrease c-Myc level. TM had limited effects on non-cancerous cells and tumor-free mice, suggesting that cancer cells have an increased dependency on SIRT2 that can be exploited for therapeutic benefit. Our studies demonstrate that SIRT2-selective inhibitors are promising anticancer agents and may represent a general strategy to target certain c-Myc-driven cancers.

publication date

  • March 14, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4811675

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2016.02.007

PubMed ID

  • 26977881

Additional Document Info

start page

  • 297

end page

  • 310

volume

  • 29

number

  • 3