Coibamide A induces mTOR-independent autophagy and cell death in human glioblastoma cells

Coibamide A is an N-methyl-stabilized depsipeptide that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups (ICBG) program based in Panama. Previous testing of coibamide A in the NCI in vitro 60 cancer cell line panel revealed a potent anti-prolifera...

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Veröffentlicht in:	PloS one 2013-06, Vol.8 (6), p.e65250
Hauptverfasser:	Hau, Andrew M, Greenwood, Jeffrey A, Löhr, Christiane V, Serrill, Jeffrey D, Proteau, Philip J, Ganley, Ian G, McPhail, Kerry L, Ishmael, Jane E
Format:	Artikel
Sprache:	eng
Schlagworte:	Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Animals Apaf-1 protein Apoptosis Apoptosis - drug effects Apoptotic Protease-Activating Factor 1 - deficiency Apoptotic Protease-Activating Factor 1 - genetics Autophagy Autophagy - drug effects Autophagy-Related Protein 5 Autophagy-Related Protein-1 Homolog Bioaccumulation Biochemistry Biodiversity Biology Brain cancer Cancer Caspase Caspase 3 - genetics Caspase 3 - metabolism Caspase-3 Cell cycle Cell Cycle Proteins Cell death Cell Line, Tumor Cyanobacteria Cytotoxicity Cytotoxins - pharmacology Depsipeptides - pharmacology Embryo fibroblasts Fibroblasts Fibroblasts - cytology Fibroblasts - drug effects Fibroblasts - metabolism Gene Expression Regulation, Neoplastic - drug effects Glioblastoma Glioblastoma cells Glioblastomas Glioma Growth factors Humans Immunoglobulins Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Kinases Mathematics Medical prognosis Medicine Melanoma Mice Microtubule-Associated Proteins - deficiency Microtubule-Associated Proteins - genetics Mitochondria Mortality Natural products Organ Specificity Phagocytosis Pharmaceutical sciences Phosphoproteins - genetics Phosphoproteins - metabolism Phosphorylation Protein Serine-Threonine Kinases - genetics Protein Serine-Threonine Kinases - metabolism Proteins Ribosomal Protein S6 Kinases - genetics Ribosomal Protein S6 Kinases - metabolism Signal Transduction - drug effects Signaling TOR protein TOR Serine-Threonine Kinases - genetics TOR Serine-Threonine Kinases - metabolism Toxicity
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Zusammenfassung:	Coibamide A is an N-methyl-stabilized depsipeptide that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups (ICBG) program based in Panama. Previous testing of coibamide A in the NCI in vitro 60 cancer cell line panel revealed a potent anti-proliferative response and "COMPARE-negative" profile indicative of a unique mechanism of action. We report that coibamide A is a more potent and efficacious cytotoxin than was previously appreciated, inducing concentration- and time-dependent cytotoxicity (EC50
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0065250