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

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. 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.