Paris polyphylla ethanol extract induces G2/M arrest and suppresses migration and invasion in bladder cancer

Abstract

Background Paris polyphylla is a traditional Chinese medicinal herb with multiple antitumor activities, but the role of P. polyphylla in bladder cancer (BC) is under investigation. This study aims to examine the antitumor activities of P. polyphylla ethanol extract (PPE) on BC cells and elucidate the underlying mechanisms. Methods Viable cells were counted using the trypan blue exclusion assay. The cell cycle was analyzed using flow cytometry, and scratch wound-healing and transwell assays were used to evaluate cell migration and invasion abilities, respectively. The protein expression levels were determined by western blotting. A xenograft model was used to assess the in vivo inhibitory effect of PPE on BC tumor growth. Results Our results showed that PPE inhibited the growth of BC cells in vivo and in vitro . Mechanistically, PPE regulated the levels of cell cycle-associated proteins, with PPE-induced G2/M phase arrest occurring through cyclin-dependent kinase inhibitor 1 (CDKN1A) accumulation and cyclin B1 (CCNB1)/cyclin-dependent kinase 1 (CDK1) inhibition. BC tumor growth was also inhibited by PPE treatment. Moreover, the migration and invasion abilities of J82 cells were suppressed through modulating epithelial-mesenchymal transition (EMT) regulatory factors with upregulation of cadherin-1 (CDH1) and downregulation of cadherin-2 (CDH2), snail family transcriptional repressor 2 (SNAI2), and twist family bHLH transcription factor 1 (TWIST1). Conclusions PPE inhibited cell growth, induced G2/M arrest, and suppressed the migration and invasion of J82 cells. BC tumor growth in vivo was also inhibited by PPE. Our results lay the foundation for further studies on the antitumor mechanisms of PPE.

Paris polyphylla Sm. Induces Reactive Oxygen Species and Caspase 3-Mediated Apoptosis in Colorectal Cancer Cells In Vitro and Potentiates the Therapeutic Significance of Fluorouracil and Cisplatin

“…The viability of the normal human colon epithelial cell line, CCD 841 CoN, upon treatment with PPE was comparatively higher compared with the cancer cell lines, showing that PPE is less toxic to the normal colon cell line. Inhibition of colony and migration in bladder cancer cell line J82 after treatment with P. polyphylla ethanol extract has been reported [ 55 ]. Paris saponin II and PP9 inhibit colony formation in HT-29 and HCT-116 cell lines [ 56 , 57 ].…”

“…A critical literature search revealed the use of the hydroalcoholic solution as a solvent for extracting P. polyphylla rhizome, which induces anticancer activity [ 17 , 44 , 55 ]. P. polyphylla rhizome was washed in running water, cut into small pieces, and shade-dried for a week.…”