Glucose 6-phosphate dehydrogenase inhibition sensitizes melanoma cells to metformin treatment.

Most cancer cells exacerbate the pentose phosphate pathway (PPP) to enhance biosynthetic precursors and antioxidant defenses. Metformin, which is used as a first-line oral drug for the treatment of type 2 diabetes, has been proposed to inhibit the malignant progression of different types of cancers. However, metformin has shown poor efficacy as single agent in several clinical trials.

Inhibition of bioenergetic metabolism by the combination of metformin and 2-deoxyglucose highly decreases viability of feline mammary carcinoma cells.

Feline mammary carcinoma (FMC) is a highly aggressive pathology that has been proposed as an interesting model of breast cancer disease, especially for the hormone refractory subgroup. Recently, cancer cell metabolism has been described as a hallmark of cancer cells. Here, we investigate the effects and mechanism of metabolic modulation by metformin (MET, anti-diabetic drug), 2-deoxyglucose (2DG, hexokinase inhibitor) or a combination of both drugs, MET/2DG on two established FMC cells lines: AlRB (HER2 (3+) and Ki67<5%) and AlRATN (HER2 (-) and Ki67>15%).