Paris saponin Ⅶ,a direct activator of AMPK,induces autophagy and exhibits therapeutic potential in non-small-cell lung cancer

摘要

Paris saponinⅦ(PSⅦ),a bioactive constituent extracted from Trillium tschonoskii Maxim.,is cytotoxic to several cancer types.This study was designed to explore whether PSⅦprevents non-small-cell lung cancer(NSCLC)proliferation and to investigate its molecular target.AMP-activated protein kinase(AMPK)has been implicated in the activation of autophagy in distinct tissues.In cultured human NSCLC cell lines,PSⅦinduces autophagy by activating AMPK and inhibiting m TOR signaling.Furthermore,PSⅦ-induced autophagy activation was reversed by the AMPK inhibitor compound C.Computational docking analysis showed that PSⅦdirectly interacted with the allosteric drug and metabolite site of AMPK to stabilize its activation.Microscale thermophoresis assay and drug affinity responsive target stability assay further confirmed the high affinity between PSⅦand AMPK.In summary,PSⅦacts as a direct AMPK activator to induce cell autophagy,which inhibits the growth of NSCLC cells.In the future,PSⅦtherapy should be applied to treat patients with NSCLC.