Bardoxolone methyl suppressed colorectal cancer cells in vitro by inhibiting the PI3K signaling pathway

The occurrence and death rates of colorectal cancer (CRC) have been consistently increasing, demanding the immediate requirement for the creation of dependable and effective medicinal treatments. This study investigates bardoxolone methyl (CDDO-Me), a synthetic triterpenoid, as a potential therapeutic agent for CRC. Integrating network pharmacology, bioinformatic analyses, and in vitro assays, we evaluated the effects of CDDO-Me on CRC cells. In vitro studies indicate that CDDO-Me significantly inhibits the growth of CRC cells, specifically HCT116 and RKO, with IC₅₀ values of 3.17 µM and 7.64 µM, respectively. Additionally, CDDO-Me effectively suppresses the PI3K signaling pathway and increases reactive oxygen species (ROS) levels in CRC cells. Consequently, this leads to G2/M phase arrest, an increase in apoptosis (over 30%), and a decrease in adhesion and invasion capabilities. Importantly, these effects were reversible upon the administration of N-acetylcysteine. Collectively, our findings provide compelling evidence for the potential of CDDO-Me as a promising candidate for the treatment of CRC.