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

ABSTRACT: Dimeric ?-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 ?-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.

SUBMITTER: Chatwichien J

PROVIDER: S-EPMC5464723 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Chatwichien Jaruwan J Basu Subhasree S Budina-Kolomets Anna A Murphy Maureen E ME Winkler Jeffrey D JD

Bioorganic & medicinal chemistry letters 20160913 20

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. ...[more]

PMID: 27650927

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