P 234 - Glut 1 overexpression prevents glucose deprivation-induced prostate cancer cell death by increasing pentose phosphate pathway and glutathione

Abstract

Although glucose metabolism was override in prostate cancer, it is recognized that there are metabolic differences between androgen-sensitive and castration-resistant phenotypes that might be responsible of progression or treatment success. Among the targets of glucose metabolism, glucose uptake is on the top of the cascade. The increase of glucose uptake by GLUTs overexpression in oncogenesis or the androgenic regulation of some GLUT transporters in other tissues is demonstrated. The prostate, at the beginning of carcinogenesis, depends on OXPHOS but then, at aggressive stages, tumors become again glycolytic like other cancers. Therefore, their resistance to glucose deprivation is different at the beginning or at later stages. In this work, we demonstrated by using androgen sensitive and insensitive cells that facilitative GLUT1 transporter overexpression protect prostate cancer cells from apoptosis caused by glucose removal. Glucose removal caused an increment in oxidative stress that stimulated androgen receptor activity and GLUT1 overexpression. This protection is mediated by a derivation towards pentose phosphate metabolic pathway and an increment of glutathione in androgen dependent prostate cancer cells.