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

Oncol Lett. 2023 Oct 5;26(6):501. doi: 10.3892/ol.2023.14088. eCollection 2023 Dec.

Abstract

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.

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

Grants and funding

The present study was supported by the Basic Research Program through the National Research Foundation of Korea (NRF) funded by MSIT (grant nos. RS-2023-00207868 and RS-2023-00247255) and the Ministry of Education (grant no. NRF-2020R1F1A1072646).