3-O-Acetylrubiarbonol B induces apoptosis of colorectal cancer cells by activating JNK/p38 MAPK and ROS generation

Colorectal cancer (CRC) continues to be a significant health issue, claiming millions of lives each year. The challenge is exacerbated by resistance to anticancer treatments, which reduces therapeutic effectiveness and calls for strategies to combat drug-resistant cancer. In this study, we explored the anticancer effects of 3- O -Acetylrubiarbonol B (ARu-B) in human CRC HCT116 cells, both with and without oxaliplatin (Ox) resistance. ARu-B effectively inhibited the growth of HCT116 cells as well as the Ox-resistant strain HCT116-OxR, as evaluated through MTT and soft-agar assays. IC 50 values were 5.4 µM and 4.0 µM in HCT116 and HCT116-OxR cells, respectively in 48-h incubation. ARu-B induced apoptosis by increasing the phosphorylation of JNK and p38 MAPK, arresting cell cycle at the G2/M phase, reactive oxygen species (ROS) generation, mitochondrial membrane potential dissipation, and caspase activation. The essential roles of JNK and p38 MAPK phosphorylation were validated by preincubating with SP600125 and SB203580. Additionally, preincubation with N-acetyl cysteine (NAC) highlighted the significant role of ROS in mediating apoptosis. The apoptotic induction via caspase activation was confirmed by the prevention of cytotoxicity following Z-VAD-FMK pretreatment. In summary, ARu-B inhibited the growth of CRC HCT116 cells effectively, regardless of Ox resistance. Future studies are anticipated to develop effective anticancer agents based on ARu-B.