title: PUMA-dependent apoptosis in NSCLC cancer cells by a dimeric β-carboline.
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.
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Jaruwan
authors.initials: J
authors.lastname: Chatwichien
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, United States.
authors.forename: Subhasree
authors.initials: S
authors.lastname: Basu
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, United States.
authors.forename: Anna
authors.initials: A
authors.lastname: Budina-Kolomets
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, United States.
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Murphy
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Winkler
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D019281:Dimerization; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D002243:Carbolines; D011518:Proto-Oncogene Proteins; C010262:norharman
keywords: Apoptosis; Autophagy; Lysosomotropic; PUMA; β-Carboline dimer