Studying the effects of Muscone on PANC-1 in vitro

Abstract: In this project cancer was viewed as a metabolic disorder. The study focused on the effect of synthetic muscone on PANC-1 cells. Synthetic muscone is a ketone. Some cancers lack the potential to metabolise ketone bodies, mainly due to mitochondrial dysfunction. The Warburg effect is a biochemical phenomenon in which cancer cells favour metabolism through glycolysis instead of oxidative phosphorylation to produce ATP. The cells were treated with various concentrations of muscone for 24 and 48 hours. Three different assays were chosen to assess the effects of the treatment. These included an MTS-Assay to estimate the cell-viability, a Lactate-Glo kit to assess the lactate production after the treatment and Caspase 3/7 assay for the apoptotic effects of the treatment. Lactate is the end product of glycolysis, thus its decrease could be an indication of an effective treatment. Instead, the lactate produced exhibited an increasing tendency. Caspase activity was increased for concentration 500μΜ, whilst no effect was noted for the remaining concentrations tested. Expression of genes involved in glycolysis (HK2, GAPDH & PKM2), apoptotic pathways (CYCS), mitochondrial function (TFAM) and ketolytic activities (BDH1 & OXCT1) were chosen to be tested for a better understanding of the results derived from the assays. The expression of CYCS was in accordance with the findings of the MTS and Caspase assays for concentration 500μΜ, making its investigation promising for future research. Due to time restrictions most experiments were conducted once, thus no safe conclusions could be reached. However, we expect this pilot study to provide valuable insight for future researchers who aim to approach cancer treatment from a metabolic perspective.