RESUMEN
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.
Asunto(s)
Neoplasias Óseas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Receptores ErbB/metabolismo , Osteosarcoma/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Humanos , Proteínas de Membrana de los Lisosomas/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Osteosarcoma/patología , Physalis/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Ten new sucrose esters, physakengoses A-J (1-10), were isolated from the aerial parts of Physalis alkekengi var. franchetii under the guidance of 1H NMR spectroscopy. Their structures were determined by spectroscopic analyses (HRESIMS, 1D and 2D NMR, and ESIMS) and chemical methods. These new compounds were tested for antibacterial activities against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli. Among them, compounds 2 and 5-8 showed potent inhibitory effects against test strains with MIC values ranging from 3.5 to 14.9µg/mL. These findings may indicate that the P. alkekengi var. franchetii has potential application as an ingredient in pharmaceuticals.