An investigation into the anticancer effects and mechanism of action of garcinone E on colorectal cancer

Abstract

Although many therapeutic approaches have been adopted, colorectal cancer (CRC) is still one of the most aggressive illnesses in the world. Developing novel and more effective methods for CRC treatment is always an important and challenging task for researchers. Mangosteen is a popular fruit in tropical areas, and it has long been utilized as an herbal remedy in Southeast Asia. The present investigation aimed to study the anticancer effects of the bioactive ingredients in mangosteen and explore their underlying mechanisms of action. Xanthones, a major bioactive compound in mangosteen, showed potent cytotoxicity against different cancer cells in our study. Among the xanthones tested, garcinone E (GAR E) possessed promising anticancer effects on CRC cell lines. Our in vitro i investigations demonstrated that GAR E could suppress AKT/mTOR and MEK/ERK signal transduction cascades to prevent cancer cell proliferation and migration. Furthermore, GAR E triggered the production of reactive oxygen species (ROS), which induced mitochondrial dysfunction and apoptosis in CRC cells, causing the arrest of cell cycle at the Sub G1 phase. Additionally, the ratio of Bax/Bcl-2 was elevated by GAR E treatment, with the activation of PARP, caspase 3 and 9, and JNK1/2. The cytotoxic activities and expressions of signaling proteins induced by GAR E treatment could be reversed by N-acetyl-L-cysteine and the JNK inhibitor SP600125, indicating the participation of an ROS/JNK-dependent mechanisms. The in vivo experiments were carried out on an HT-29 colorectal carcinoma cell xenografted nude mouse model and a significant antitumor effect of GAR E was observed. In conclusion, our study has shown that GAR E is potentially effective in treating CRC and has given us some insights into developing xanthones as novel chemotherapeutic agents.