TARGETING GLUCOSE METABOLISM FOR THE TREATMENT OF GLIOBLASTOMA

ARBE, MARÍA FLORENCIA; PAN, MELISA; BELGOROSKY, D; EIJAN AM.; GOMEZ ESCALANTE, JOSE; MOUGHTY, CAROLINA; ZALLOF , JUAN; MAZZON, ALEJANDRO; PROST, DIEGO; GLIKIN, GC; FINNOCHIARO, LME; VILLAVERDE M. S.

Congreso; Reunion Anual SAIB 2019; 2019

Glioblastoma (GBM) has the highest incidence among primary brain cancers and is also associated with poor prognosis. As in many other types of cancers, glycolysis and pentose phosphate pathway (PPP) support GBM proliferation and contributes to cancer development. Metformin (MET) is used as first-line oral drug for the treatment of Type 2 Diabetes Mellitus (T2MD). Interestingly, MET can efficiently inhibit progression of oral premalignant lesions and diminish tumor growth in different types of xenografts cancer models, including GBM. Here, we combined MET with 2DG, which is a glucose analog that inhibits Hexokinase (HK, the first and limiting enzyme of glycolysis), or with 6-aminonicotinamide (6AN) , which is a Glucose-6 phosphate dehydrogenase (G6PD, the first and limiting enzyme of PPP) in 3 well characterized human GBM cell lines, U87, U373 and U251. We found that 2DG decreased the viability (APH assay, p