Piper longum Constituents Induce PANC‐1 Human Pancreatic Cancer Cell Death under Nutrition Starvation

Abstract

Pancreatic cancer is a highly aggressive form of cancer with a poor prognosis, partly due to ‘austerity’, a phenomenon of tolerance to nutrient deprivation and survival in its hypovascular tumor microenvironment. Anti‐austerity agents which preferentially diminish the surivival of cancer cells under nutrition starvation is regarded as new generation anti‐cancer agents. This study investigated the potential of Piper longum constituents as anti‐austerity agents. The ethanolic extract of Piper longum was found to have preferential cytotoxicity towards PANC‐1 human pancreatic cancer cells in a nutrient‐deprived medium (NDM). Further investigation led to the identification of pipernonaline (3) as the lead compound with the strongest anti‐austerity activity, inducing cell death and inhibiting migration in a normal nutrient medium, as well as strongly inhibiting the Akt/mTOR/autophagy pathway. Therefore, pipernonaline (3) holds promise as a novel antiausterity agent for the treatment of pancreatic cancer.