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. Epub 2016 Sep 13.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / physiology*
  • Carbolines / chemistry
  • Carbolines / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Dimerization
  • Humans
  • Lung Neoplasms / pathology*
  • Proto-Oncogene Proteins / physiology*

Substances

  • Apoptosis Regulatory Proteins
  • BBC3 protein, human
  • Carbolines
  • Proto-Oncogene Proteins
  • norharman