Unknown,Transcriptomics,Genomics,Proteomics

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Demethyl fructiculin A (SCO-1) induces apoptosis by inducing reactive oxygen species in mitochondria

ABSTRACT: Demethyl fructiculin A is a diterpenoid quinone component of the exudates from Salvia corrugata (SCO-1) leafes. SCO-1 was recently reported to induce anoikis in mammalian cell lines via a molecular mechanism involving the presence of the membrane scavenging receptor CD36. However, experiments performed with cells lacking CD36, showed that SCO-1 was able to induce apoptosis also via alternate pathways. To contribute to a better characterization of the molecular mechanisms underlining the cytotoxic activity of SCO-1, we decided to pursue an unbiased pharmacogenomic approach by generating the gene expression profile of GBM TICs subjected to the administration of SCO-1 and comparing it with that of control cells exposed to the solvent. With this strategy we hypothesized to highlight those pathways and biological processes unlashed by SCO-1. Using this approach we unveiled that the main mechanism responsible for the SCO-1 pro-apoptotic effect is superoxide generation in mitochondria and that this molecule has potential chemotherapeutic properties that should be further investigated in GBM xenotransplant models. To get an insight on the biological processes and pathways elicited by Demethyl fructiculin A (SCO-1), we undertake an unbiased genomic approach in order to identify genes deregulated by SCO-1. Cells were treated with 9.3 Î¼g/ml concentration (IC50 at 48h) or vehicle alone (DMSO) and kept in a humidified 5% CO2 atmosphere at 37Â°C for the indicated time period (24 or 48 hours). After 24 hours of exposure of glioblastoma tumor initiating cells (GBM TICs) to SCO-1, we found the deregulation of genes belonging to the Glutathione metabolism pathway and of those belonging to the biological processes related to the response to stress and chemical stimulus.

ORGANISM(S): Homo sapiens

SUBMITTER: Antonio Daga

PROVIDER: E-GEOD-19846 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Demethyl fruticulin A (SCO-1) causes apoptosis by inducing reactive oxygen species in mitochondria.

Monticone Massimiliano M Bisio Angela A Daga Antonio A Giannoni Paolo P Giaretti Walter W Maffei Massimo M Pfeffer Ulrich U Romeo Francesco F Quarto Rodolfo R Romussi Giovanni G Corte Giorgio G Castagnola Patrizio P

Journal of cellular biochemistry 20101201 5

Demethyl fruticulin A (SCO-1) is a compound found in Salvia corrugata leaves. SCO-1 was reported to induce anoikis in cell lines via the membrane scavenging receptor CD36. However, experiments performed with cells lacking CD36 showed that SCO-1 was able to induce apoptosis also via alternative pathways. To gain some insight into the biological processes elicited by this compound, we undertook an unbiased genomic approach. Upon exposure of glioblastoma tumor initiating cells (GBM TICs) to SCO-1 f ...[more]

PMID: 20683904

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