Abstract
Paris polyphylla. is a traditional medicinal herb that has long been used to prevent cancer in many Asian countries. Polyphyllin I (PPI), an important bioactive constituent of Paris polyphylla, has been found to exhibit a wide variety of anticancer activities in many types of cancer cells. However, the effects of PPI on human gastric carcinoma cells and its mechanism of action remain unclear. In this study, we examined the effective anti-gastric carcinoma activity of PPI and its underlying mechanism of action in HGC-27 cells. In vitro, sub-micromolar concentrations of PPI inhibited HGC-27 cell proliferation with an IC50 of 0.34 ± 0.06 μM after a 72-h treatment. In vivo, 3 mg/kg PPI significantly inhibited proliferation of HGC-27 tumor cells, with a 78.8% inhibition rate compared to paclitaxel, and demonstrated higher safety. Analysis of MDC and mGFP-LC3 fluorescence, Western blotting and flow cytometry indicated that PPI induced cell cycle arrest in HGC-27 cells by promoting the conversion of LC3-I to LC3-II and by downregulating cyclin B1. Furthermore, Western blotting showed that PPI inhibited the autophagy-regulating PDK1/Akt/mTOR signaling pathway in vitro and in vivo. In addition, immunohistochemistry and TUNEL staining revealed that PPI decreased Ki67 expression and increased the percentage of apoptotic cells in HGC-27 xenograft tumors. These data indicate that PPI is an PDK1/Akt/mTOR signaling inhibitor and of therapeutic relevance for gastric cancer treatment and that the rhizome of Paris polyphylla deserves further clinical investigation as an alternative therapy for gastric cancer.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.