ABSTRACT
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer (NSCLC). CIP2A plays an 'oncogenic nexus' to participate in the tumorigenesis and chemoresistance in several cancer types. AKT and mTORC1 overactivation are detected in NSCLC and many other cancers. Previous studies found that the CIP2A/AKT/mTOR pathway controls cell growth, apoptosis, autophagy process. Polyphyllin I (PPI) and polyphyllin VII (PPVII) are natural components extracted from Paris polyphylla that display anti-cancer properties. In the present study, we investigated whether PPI and PPVII can be used in the cisplatin (DDP)-resistant human NSCLC cell line A549/DDP. Results demonstrated that PPI and PPVII treatment significantly suppressed A549/DDP cell proliferation, migration, invasion and EMT, induced apoptosis and autophagy. Further examination of the mechanism revealed that the PPI and PPVII significantly upregulated the p53, induced caspase-dependent apoptosis and suppressed the CIP2A/AKT/mTOR pathway. The activation of autophagy was mediated through PPI and PPVII induced inhibition of mTOR. We propose that PPI and PPVII might be developed as candidate drugs for DDP-resistant NSCLC.
ABSTRACT
Objective Mining Paris resources with medicinal value could underlay the breeding selection and relieve the pressure on wild resources. Methods Twenty-one Paris resources in the mountain area of Sichuan Basin were collected and selected according to their phenotype and rhizome features. Two resources GQ, MH with bigger rhizome and one resource (GK) with polygemmic feature were screened. After preliminary identification, based on Kimura-2-parameter model, molecular phylogenetic trees were constructed based on the different sequence of ITS and psbA-trnH between the screened resources and the homologous sequences from NCBI using the Maximum Like (ML) method. Main active saponin was determinated by HPLC method to predict its potential medicinal value. Results GQ, GK, and MH were special resources of P. polyphylla var. chinensis, P. polyphylla var. yunnanensis, and P. forrestii, respectively, in mountains around Sichuan Basin. The content and proportion of polyphyllin I, II, VI, VII in GQ, GK, MH were different. The total content was GQ > MH > CK > GK. The proportion of polyphyllin I in GQ and MH was 67.61% and 73.25% higher than CK, respectively. While the proportion of polyphyllin VII was most in GK (56.38%). Conclusion This study specified three Sichuan local Paris resources with excellent rhizome features. And they performed well after introduced to Chengdu Plain providing the material basis for the follow-up breeding study of Paris. Three resources have medicinal potential, especially the polyphyllin I and polyphyllin content in MH (P. forrestii) is higher, which can provide a new choice for screening substitution materials of P. polyphylla var. chinensis and P. polyphylla var. yunnanensis.