Horizon Discovery announced today that it will be presenting a joint-poster with Biolog Inc at the Symposia on Cancer Research 2009; Cellular Energy, Metabolism and Cancer to be held April 3–4, 2009 at The University of Texas M. D. Anderson Cancer Center.
The poster combined their proprietary X-MAN and Phenotype Microarray technologies to elucidate the changes in cellular energy metabolism engendered by a cancer-associated gain-of-function mutation in the PI3K gene as compared to a matched normal parental.
The study found that the parental cell line metabolized 17 or the 91 different biochemical substrates in the Biolog PM-M1 panel. The two clonal mutant PI3K cell lines show a consistent shift in cellular energy metabolism. Metabolic rates in the PI3K mutant cell lines were decreased for phosphorylated sugars (G-6-PO4, G-1-PO4, F-6-PO4) and for galactose, adenosine, inosine, chondroitin-SO4, and butyric acid. Rates were slightly increased for dextrin, glycogen, and maltose. Rates were unchanged for other utilized substrates: glucose, mannose, fructose, turanose, 3-O-methyl-glucose, and maltotriose.
These experiments demonstrate the potential of using the scope and precision of PM metabolic assays with defined cancer vs normal genotype specific readout of X-MAN isogenic human cells lines; engineered to contain selected patient-relevant cancer mutations. By testing a larger set of mutations, both singly and in combination, in various host cell lines that model different tumors, it should now be possible to gain a detailed understanding of the relationship of cancer genotype with altered energy metabolism. In the present study, the tantalizing observation that buyrate is ultilized at a much lower rate; and appears to negative effects on cell-survival, is now being studied further to determine whether A) this is a consistent phenomenon in cancers carrying activated PI3K; and B) the mechanism for this effect, such as HDAC inhibition.