Euscaphic Acid from Rosa roxburghii Tratt Exerts Anti-colorectal Cancer Activity by Inducing Mitochondrial Apoptosis through ROS/MAPK Pathway.

objectiveTo investigate the anti-colorectal cancer (CRC) activity and its potential molecular mechanism of euscaphic acid (EA), a triterpene component from Rosa roxburghii Tratt (RRT), in vitro and in vivo.

methodsEA in RRT was isolated and analyzed for pharmacophore-based virtual screening, and enrichment analysis was performed. HCT116 and CT26 cells were used for in vitro experiments. Meanwhile, we constructed a CT26 syngeneic tumor BALB/c mice model and performed in vivo experiments. Finally, the mitochondrial apoptosis and reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK) signaling pathway-related proteins were detected by Western blot.

resultsEA could inhibit the viability of HCT116 and CT26 cell lines, suppress the biological behaviors including proliferation, migration, and invasion, and induce apoptosis in vitro (P<0.05 or P<0.01). Meanwhile, in vivo experiments showed that EA significantly inhibited the growth of CRC graft tumors (P<0.05 or P<0.01). EA could decrease mitochondrial membrane potential and increase caspase-3/9 activities (P<0.05 or P<0.01). Furthermore, EA promoted the cellular ROS accumulation accompanied by activation of the MAPK signaling pathway, and interestingly, the phosphorylation level of extracellular regulated protein kinases (ERK) was higher (P<0.05 or P<0.01). In addition, the above process could be reversed by the free radical scavenger N-acetylcysteine (P<0.05 or P<0.01).

conclusionsEA could inhibit the growth of CRC cell lines both in vitro and in vivo, and activate the mitochondrial pathway through the ROS/MAPK signaling pathway to induce apoptosis in CRC cell lines. This supports the antitumor potential of triterpene acids from RRT.