A New Anti-Austerity Agent, 4 '-O-Methylgrynullarin From Derris Scandens Induces Panc-1 Human Pancreatic Cancer Cell Death Under Nutrition Starvation Via Inhibition Of Akt/Mtor Pathway

An ethanolic extract of Derris scandens flowers showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived condition, with a PC50 value of 0.7 mu g/mL. Phytochemical investigation of this active extract led to the isolation of four prenylated isoflavones (1-4) including a new compound named 4 '-O-methylgrynullarin (1). The structure elucidation of the new compound was achieved by HRFABMS and NMR spectroscopic analysis. The isolated compounds exhibited potent anti-austerity activity against four different human pancreatic cancer cell lines under nutrient-deprived conditions. The new compound 4 '-O-methylgrynullarin (1) was also found to inhibit PANC-1 cell migration and colony formation under nutrientrich condition. Mechanistically, compound 1 inhibited key survival proteins in the Akt/mTOR signaling pathway. Therefore, 4 '-O-methylgrynullarin (1) can be considered as a potential lead compound for the anticancer drug development based on the anti-austerity strategy.