Peniciketal A, A Novel Spiroketal Compound, Exerts Anticancer Effects by Inhibiting Cell Proliferation, Migration and Invasion of A549 Lung Cancer Cells

Abstract

Background: Peniciketal A (Pe-A) is a spiroketal compound isolated from saline soil-derived fungus Penicillium raistrickii. However, its role for biological processes has not been clarified. In this study, we for the first time investigated the anticancer effects and the underlying mechanisms of Pe-A in A549 lung cancer cells. Metheds: Cell proliferation was tested by MTT assay and colony formation assay. Flow cytometry was performed to examine the cell cycle, apoptosis and mitochondrial membrane potential. Invasion and migration were analyzed using transwell assay and wound healing analysis. Immunofluorescence staining and western blotting were used to evaluate the protein expression. Results: Pe-A effectively inhibited proliferation, with IC50 values was 22.33 μM for 72 h. Mechanistic studies revealed that Pe-A caused cell cycle arrest at the G0-G1 phase by decreasing cyclinD1 expression and induced apoptosis through accelerating the mitochondrial apoptotic pathway. Moreover, Pe-A significantly inhibited A549 cell migration and invasion by reducing the protein levels of MMP-2 and MMP-9, while the Epithelial- Mesenchymal Transition (EMT) property was also changed. Importantly, Pe-A exhibited much lower toxicity towards L02, normal liver cells, and MRC5, normal fibroblast cells, compared to A549 cells. Conclusion: Collectively, the current results indicate that Pe-A may offer effective potentials and insights for lung cancer treatment and drug design.