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| Status |
Public on Oct 15, 2010 |
| Title |
Demethyl fructiculin A (SCO-1) induces apoptosis by inducing reactive oxygen species in mitochondria |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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 μg/ml concentration (IC50 at 48h) or vehicle alone (DMSO) and kept in a humidified 5% CO2 atmosphere at 37°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.
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| Contributor(s) |
Monticone M, Bisio A, Daga A, Giannoni P, Maffei M, Pfeffer U, Romeo F, Quarto R, Corte G, Castagnola P |
| Citation(s) |
20683904 |
| Submission date |
Jan 12, 2010 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Massimiliano Monticone |
| E-mail(s) |
massimiliano.monticone@istge.it
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| Organization name |
IRCCS AOU San Martino – IST, Genova
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| Lab |
S.S. Biofisica e Citometria
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| Street address |
Largo R. Benzi, 10
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| City |
Genova (GE) |
| ZIP/Postal code |
16132 |
| Country |
Italy |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA122071 |
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