Salinomycin: Antitumoral Effects and Gene Expression in Neuroblastoma Cells
Priya Weerasinghe, Maximilan L Buja, Robert E Brown. UT Health Medical School, Houston, TX
Background: Salinomycin, an anticoccidial agent used in the poultry industry, has recently been identified as an anticancer stem cell agent by high-throughput screening and shown to have efficacy against breast cancer stem cells.
Design: This study was designed to assess the involvement of molecular cell death pathways in salinomycin-treated human neuroblastoma (SK-N-A-S) cells. Preliminary results indicated that salinomycin was capable of inducing apoptosis and autophagy in neuroblastoma cells.
Results: Dose-response studies, followed by TUNEL and LC3 assays confirming apoptosis and autophagy respectively, indicated that salinomycin at concentratrations of 5 µM for 24 hours induced apoptotic and autophagic cell death. High density oligonucleotide microarray analysis and validation by q RT-PCR of salinomycin-induced apoptosis and autophagy showed an increased expression of cell death-related genes at 12 hours of drug exposure. Furthermore, direct comparison of expression patterns showed 158 apoptosis-related genes versus 19 autophagy-related genes.
Conclusions: These data suggest that salinomycin might be affecting signaling of apoptosis- and autophagy-related genes with a preponderance of known apoptosis genes. Also the high number of probes altered suggests the involvement of multiple signaling pathways during salinomycin treatment. The increase in the number of probes altered at the 12 and 24 hour time points suggest more widespread cellular activation, including survival and death signaling, at longer exposures in this human neuroblastoma cell line.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 287, Tuesday Morning