PUMA-dependent apoptosis in NSCLC cancer cells by a dimeric β-carboline

  • Bioorg Med Chem Lett. 2016 Oct 15;26(20):4884-4887. doi: 10.1016/j.bmcl.2016.09.030.
Jaruwan Chatwichien  1 ,  Subhasree Basu  2 ,  Anna Budina-Kolomets  2 ,  Maureen E Murphy  2 ,  Jeffrey D Winkler  1
Affiliations
  • 1. Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, United States.
  • 2. The Wistar Institute, Philadelphia, PA 19104, United States.
PMID: 27650927 DOI: 10.1016/j.bmcl.2016.09.030
Abstract

Dimeric β-carbolines are cytotoxic against multiple NSCLC cell lines, and we report herein our preliminary studies on the mechanism of action of these dimeric structures. Dimeric β-carboline 1, which is more potent than the corresponding monomer in NSCLC cell lines, is a lysosomotropic agent that inhibits Autophagy and mediates cell death by Apoptosis, upregulating the pro-apoptotic BH3-only protein PUMA (p53 upregulated modulator of Apoptosis) in a dose dependent manner.

Keywords
Apoptosis; Autophagy; Lysosomotropic; PUMA; β-Carboline dimer.