Starving advanced prostate cancer cells by pharmacological gluose deprivation with a resveratrol trimer trans-Gnetin H [TGH]

Prostate cancer is a unique disease from a metabolic perspective. Early stage localized prostate cancer does not typically display increased aerobic glycolysis (the Warburg effect), as seen in other malignancies. However, increasing evidence suggests that advanced prostate cancer exhibits the Warburg effect and displays high glucose uptake. We describe here that trans-gnetin H (TGH), a naturally-occurring resveratrol trimer extracted from Paeonia suffruticosa, displays significant anti-cancer effects in advanced prostate cancer cells in vitro. TGH perturbs energy metabolism by blocking the availability of glucose, inducing unfolded protein response (UPR) and C-MYC pathway downregulation in PC-3 cells. Our studies demonstrate the feasibility of targeting aerobic glucose metabolism in advanced prostate cancer and identify TGH as a potential therapeutic candidate. Overall design: PC-3 treated with 2.5µM TGH for 24 hours in triplicates, PC-3 treated with DMSO as controls in triplicates