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

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 xenografted PC-3 cells in vivo.TGH perturbs energy metabolism by blocking the availability of glucose and inducing profound metabolic and transcriptomic changes in prostate cancer cells as demonstrated by RNA-seq. C-MYC, a known driver oncogene in prostate cancer, is downregulated in TGH-treated 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: PC3 xenograft tumor performed on athymic nude mice. 9 were treated with TGH. 9 were treated with vehicle control