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

[OBJECTIVE] To 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.

[METHODS] EA 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.

[RESULTS] EA 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).

[CONCLUSIONS] EA 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.