Abstract
Background: Paris polyphylla is a traditional Chinese medicinal herb that has been used as a haemostatic, antimicrobial and anticancer agent. Gastric cancer (GC) is a global health problem, with more than 1 million people newly diagnosed with gastric cancer worldwide each year.Methods: The MTT and colony formation assay were used to test the anti-proliferative effects of PP-26 on MGC-803 and BGC-823 cells. Flow cytometry assays, Hoechst 33258 staining assay and Caspase inhibitor Z-VAD-FMK were used to test apoptosis. JC-1 staining used to measure changes in mitochondrial membrane potential and western blot analysis were used to test apoptotic and PI3K/Akt pathway related proteins.Results: PP-26 had a dose-dependent inhibitory effect on the proliferation of MGC-803 and BGC-823 cells, but had no obvious anti-proliferative effect on normal liver LO2 cells and normal embryonic kidney HEK-293 cells. Additionally, PP-26 induced typical apoptotic morphological changes, such as nuclear pyknosis, nuclear cracking and apoptotic bodies. Moreover, PP-26 induced a decrease in mitochondrial membrane potential. And PP-26 modulated the expression of Bcl-xL, Mcl-1, Bax, caspase-9/-3 and PARP proteins and induced cell apoptosis through the mitochondrial apoptotic pathway. Next, using an irreversible general caspase inhibitor (Z-VAD-FMK), we confirmed the activation of the mitochondrial apoptotic pathway induced by PP-26. Furthermore, PP-26 inhibited the phosphorylation of Akt and GSK-3β. The inhibition of Akt protein activated the mitochondrial apoptotic pathway.Conclusion: Collectively, these results indicated that PP-26 inhibited the proliferation of MGC-803 and BGC-823 cells by inhibiting the Akt signalling pathway and activating the mitochondrial apoptotic pathway.
Astragaloside IV Inhibits Doxorubicin-Induced Cardiomyocyte Apoptosis Mediated by Mitochondrial Apoptotic Pathway via Activating the PI3K/Akt Pathway
