Abstract

Background Physakengose G (PG) is a new compound first isolated from Physalis alkekengi var. franchetii , an anticarcinogenic traditional Chinese medicine . PG has shown promising anti-tumor effects, but its underlying mechanisms remain unknown. Purpose To investigate the anti-cancer effects of PG on human osteosarcoma cells and the underlying mechanisms. Methods Cell viability was measured by MTT assay . Apoptosis rates, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and acidic vesicular organelles (AVOs) formation were determined by flow cytometry. Protein levels were analyzed by immunofluorescence and western blotting . Results PG inhibited cell proliferation and induced apoptosis in human osteosarcoma cells. PG treatment blocked EGFR phosphorylation and suppressed epidermal growth factor (EGF)-induced activation of downstream signaling molecules, such as AKT and mTOR . PG treatment resulted in lysosome dysfunction by altering lysosome acidification and LAMP1 levels, which led to autophagosome accumulation and autophagic flux inhibition. Conclusion PG inhibits cell proliferation and EGFR/mTOR signaling in human osteosarcoma cells. Moreover, PG induces apoptosis through the mitochondrial pathway and impedes autophagic flux via lysosome dysfunction. Our findings indicate that PG has the potential to play a significant role in the treatment of osteosarcoma.