Human colorectal cancer (CRC) is a major cause of cancer morbidity and mortality, and its incidence rates are increasing in economical transitioning areas globally. To develop efficient chemotherapy drugs for CRC, the present study isolated and identified a novel ent-kaurane diterpenoid from Pteris semipinnata, termed pterisolic acid G (PAG). This ent-kaurane diterpenoid was demonstrated to significantly inhibit the growth of human CRC HCT116 cells in a time- and dose-dependent manner, determined using the Cell Counting Kit-8 assay. Additionally, western blot analysis, Hoechst 33342 staining and cytometry analysis revealed that PAG not only inhibited the viability of HCT116 cells by suppressing the dishevelled segment polarity protein 2/glycogen synthase kinase 3 β/β-catenin pathway, but also induced the apoptosis of HCT116 cells by downregulating nuclear factor-κB p65 activity, stimulating p53 expression and promoting the generation of intracellular reactive oxygen species. These results suggest that PAG, a novel inhibitor of the Wnt/β-catenin pathway and inducer of apoptosis, should be investigated in more detail using in vivo experiments and comprehensive mechanistic studies in order to examine the potential use of PAG as a novel therapeutic agent for the treatment of CRC.
Keywords: Wnt/β-catenin pathway; apoptosis; ent-kaurane diterpenoid; pterisolic acid G; viability.