2. Academic Validation
  3. PUMA-dependent apoptosis in NSCLC cancer cells by a dimeric β-carboline

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

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.

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