A pentacyclic triterpene derivative possessing polyhydroxyl ring A suppresses growth of HeLa cells by reactive oxygen species-dependent NF-κB pathway

Abstract

Pentacyclic triterpene derivatives possessing polyhydroxyl ring A exhibit many important pharmacological activities. (1β, 2α, 3β, 19β, 23)−1,2,3,19,23-pentahydroxyolean-12-en-28-oic acid (5), a new bioactive phytochemical with tetra-hydroxyl ring A isolated from Euphorbia sieboldiana in our laboratory, showed potential inhibition effects against several cancer cells previously. This study was performed to investigate the underlying mechanisms of action for its antitumor activity. The results showed that compound 5 inhibited dose-/time-dependently cell growth with low toxicity to normal cells and induced apoptosis in cervical cancer cells. Also, compound 5 inhibited the growth and proliferation of HeLa cells and resulted in G1 phase arrest. Furthermore, exposure of cells to compound 5 caused inactivation of the TNF-α–TAK1–IKK-NF-κB axis and inhibition of TNF-α–stimulated NF-κB activity, followed by down-regulation of NF-κB target genes involved in cell apoptosis (Bcl-2) and in the cell cycle and growth (Cyclin D, c-Myc). Additionally, compound 5 significantly suppressed the migration of HeLa cells. In addition, exposure of HeLa cells to compound 5 decreased the activity of NF-κB through the generation of reactive oxygen species (ROS). Collectively, these results suggested that compound 5 exerted potent anticancer effects on HeLa cells in vitro through targeting the ROS-dependent NF-κB signaling cascade and this compound may be a promising anticancer agent for cancer treatment.