#38 Targeting cell signaling pathways with a commonly used FDA-approved Drug for Medullablastoma Brain Tumor
Sandhini Lockman, Regenerative Medicine; Annan Ali Sher, Regenerative Medicine; Kimia Sheikholeslami, Regenerative Medicine; Daniel Kroft, Regenerative Medicine; Marjorie Buist, Regenerative Medicine; Shayan Amiri, Regenerative Medicine; Shahla Shojaei, Regenerative Medicine; Saeid Ghavami, Regenerative Medicine; Mojgan Rastegar, Regenerative Medicine
Recent evidence links SKAD2; a commonly used FDA-approved drug as a therapeutic for cancer based on its effect on metabolic signaling. However, its potential anti-cancer effects have not been elucidated on Medullablastoma. It is suggested the drug controls the Adenosine Monophosphate-activated Protein Kinase (AMPK) signalling cascade triggered by the LKB1 serine/threonine kinase, which results in the inhibition of gluconeogenesis. If there is a mutation in this pathway, the cancerous cells may be more susceptible to this drug resulting in cell death. Hypothesis: SKAD2 leads to targeted death of cancerous cells in the brain.
Three Medullablastoma derived cell lines were purchased from ATCC. Cells were grown in culture and treated with five different doses of SKAD2. Cell viability was quantified via MTT assay. Drug dosage that resulted in approximately 30-50% cell viability after 48-72 hours was selected in order to treat the cells to perform Caspase-3/7, -8, -9 (caspase Glo Luminescence assay) and propidium iodide flow cytometry apoptosis assay (Nicoletti Assay). The data was analyzed using one-way ANOVA analysis comparing each drug dosage dependent treatment to its control group.
After 48 hours post-treatment with 500 uM SKAD2, the Daoy, SHH-dependent brain tumour, cell line displayed a significant in cell viability with a p value of 0.0001. Conversely, two Medullablastoma group 3 cell lines; D283 and D341 cells did not display a significant decrease in cell viability. Furthermore a significant decrease in both the Caspase 3/7 and 9 was observed solely in the Daoy cells after 72 hours post treatment with SKAD2.
SKAD2 has the potential to be a novel anti-cancer drug depending on the subgroup of medullablastoma it is being used to treat. For instance, the SHH subgroup commonly observed in infants (0-3 years) diagnosed with Medullablastoma, due to its possible modulating affect on the AMPK pathway.