Premna puberula root petroleum ether extract inhibits proliferation, migration and invasion, and induces apoptosis through mitochondrial pathway in non-small cell lung cancer A549 cells

Abstract

Premna puberula, a medicine food homologous plant, is utilized in the preparation of cold tofu and as traditional Chinese medicine. This study aimed to identify the chemical components of P. puberula root petroleum ether extract (PEE) and clarify its anticancer properties and associated mechanisms. The MTT results of the four extracts (petroleum ether extract, ethyl acetate extract, n-butanol extract, and water extract) from P. puberula root showed that the PEE had good cytotoxic activity against A549 cells (IC50 = 38.01 ± 3.36 μg/mL) and low toxicity to normal cells (IC50 = 76.85 ± 3.18 μg/mL). The GC-FID/MS analysis revealed fifty compounds, which made up 98.6 % of the total PEE. Further antitumor assay demonstrated that PEE induced cell cycle arrest in the S phase by up-regulating p21 and cyclin E2 expression, thereby inhibiting the proliferation of A549 cells. Simultaneously, it induces apoptosis through the mitochondrial-mediated apoptosis pathway, which significantly up-regulated the ratio of Bax/Bcl-2, down-regulated mitochondrial membrane potential (ΔΨm), promoted the release of Cyt c, activated caspase-9 and caspase-3, thereby resulting in PARP cleavage. It prevented the migration and invasion of A549 cells by reducing the expression of MMP-2 and N-cadherin. In conclusion, P. puberula root PEE can be a new source of antitumor agents and has significant anticancer activity in vitro.