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. PC-3 treated with 2.5µM TGH for 24 hours in triplicates, PC-3 treated with DMSO as controls in triplicates

从代谢视角来看，前列腺癌是一类独具特征的疾病。早期局限性前列腺癌通常不会如其他恶性肿瘤一般表现出有氧糖酵解（Warburg effect，瓦博格效应），但越来越多的研究证据表明，晚期前列腺癌会呈现瓦博格效应，并具备高葡萄糖摄取能力。本研究报道，反式藤黄菌素H（TGH）——一种从牡丹（Paeonia suffruticosa）中提取的天然白藜芦醇三聚体——在体外实验中对晚期前列腺癌细胞展现出显著的抗癌活性。TGH可通过阻断葡萄糖的可利用性，诱导PC-3细胞发生未折叠蛋白反应（UPR）并下调C-MYC通路，从而干扰细胞能量代谢。本研究证实了靶向晚期前列腺癌有氧糖代谢的可行性，并确定TGH是一款潜在的治疗候选药物。以2.5μM TGH处理PC-3细胞24小时，设置三组生物学重复；以二甲基亚砜（DMSO）处理PC-3细胞作为对照组，同样设置三组生物学重复。