Sakurasosaponin inhibits lung cancer cell proliferation by inducing autophagy via AMPK activation

Sakurasosaponin (S-saponin; PubChem ID: 3085160), a recently identified saponin from the roots of Primula sieboldii, has shown potential Anticancer properties against various types of Cancer. In the present study, the effects of S-saponin on non-small cell lung Cancer (NSCLC) cell proliferation and the underlying mechanisms, were investigated. The effect of S-saponin on cell proliferation and cell death were assessed CCK-8, clonogenic assay, western blotting and Annexin V/PI double staining. S-saponin-induced Autophagy was determined by confocal microscopic analysis and immunoblotting. S-saponin inhibited the proliferation of A549 and H1299 NSCLC cell lines in a dose- and time-dependent manner, without inducing Apoptosis. S-saponin treatment induced Autophagy in these cells, as evidenced by the increased LC3-II levels and GFP-LC3 puncta formation. It activated the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which is crucial for Autophagy induction. Inhibition of AMPK with Compound C or siRNA-mediated knockdown of AMPK abrogated S-saponin-induced Autophagy and partially rescued cell proliferation. Therefore, S-saponin exerts anti-proliferative effects on NSCLC cells through Autophagy induction via AMPK activation. Understanding the molecular mechanisms underlying the Anticancer effects of S-saponin in NSCLC cells could provide insights for the development of novel therapeutic strategies for NSCLC.

adenosine monophosphate-activated protein kinase; autophagy; cell proliferation; non-small cell lung cancer; sakurasosaponin.