Fig. 5.

Metabolic profile changes associated with CHS and MET treatment in mutant K-ras (MIA PaCa-2) PDAC cell lines. At baseline, the mutant K-ras cancer cells exhibit less efficient glucose oxidation and low fatty acid synthase flux with cholesterol readily synthesized. CHS treatment (green) blocks cholesterol synthesis, by which glucose-deriving acetyl-CoA is diverted towards fatty acid synthase, instead of new cholesterol synthesis. This is when addition of metformin (red) gains a functional fatty acid synthase inhibitory effect. This demonstrates the contextual System effects of mutated K-ras, cholesterol and metformin in the metabolic syndrome to inhibit potentially membrane production and cancer growth. Please note that hypotheses for further testing are suggested as (1) the effect of CHS on glut-aminotransferase, (2) further evidence for MET inhibition of the citrate arm of the TCA cycle and (3) pyruvate carboxylase, which is only significant in the presence of CHS