Unveil the mechanism for EHMT -- A novel triterpenoid inhibits proliferation and induces apoptosis in colon cancer through ROS-mediated JNK signaling pathway - 27/04/24
Abstract |
Colon cancer ranks among the most prevalent malignancies worldwide, trailing only lung and breast cancer in incidence. Despite the availability of numerous therapeutic strategies, the burden of new cases and fatalities remains high in countries undergoing socioeconomic transitions. Natural products offer promising avenues for developing more effective and less toxic anticancer agents, expanding the clinical arsenal. In this investigation, we isolated a triterpenoid, (21 S,23 R,24 R)-21,23-epoxy-24-hydroxy-21-methoxytirucalla-7,25-dien-3-one (EHMT), from the fruits of Melia azedarach L., which exhibited significant inhibitory activity against colon cancer cells while sparing normal cells. EHMT effectively curtailed colony formation and induced apoptosis and cell cycle arrest in the HCT116 cell line. Furthermore, EHMT prompted the generation of reactive oxygen species (ROS) and the depolarization of mitochondrial membrane potential. Notably, EHMT treatment triggered ROS-mediated cell apoptosis via activation of the JNK signaling pathway in HCT116 cells. Additionally, our findings extended to Caenorhabditis elegans, where EHMT induced ROS accumulation and apoptosis. Collectively, these findings position EHMT as a promising candidate for the development of anticancer agents in the treatment of colon cancer, offering new hope in the battle against this formidable disease.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
(21 S,23 R,24 R)-21,23-epoxy-24-hydroxy-21-methoxytirucalla-7,25-dien-3-one (EHMT) was isolated from the fruit of M. azedarach L. EHMT caused ROS generation and induces apoptosis both in vivo and in vitro, triggered ROS-modulated cell apoptosis associated with JNK signaling pathway activation in colon cancer cells.
Le texte complet de cet article est disponible en PDF.Highlights |
• | Natural products represent the biggest source of small molecules, providing a great potential to develop new anticancer agents. |
• | EHMT, a novel anit-cancer triterpenoid isolated from Melia azedarach L. fruits, triggers ROS-modulated cell apoptosis and activates the JNK signaling pathway in colon cancer cells. |
• | EHMT demonstrates a pronounced ability to inhibit the proliferation of colon cancer cells while exerting minimal impact on normal colon cells. |
• | The findings in this study shed light on the potential of EHMT as a promising candidate for colon cancer therapy. |
Keywords : Triterpenoid, Apoptosis, ROS, JNK pathways, Colon cancer, Natural products
Plan
Vol 174
Article 116469- mai 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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