Evodiamine Induces Apoptosis, G2/M Cell Cycle Arrest, and Inhibition of Cell Migration and Invasion in Human Osteosarcoma Cells via Raf/MEK/ERK Signalling Pathway
Yuelai Zhou, Jinlong Hu
(Department of Orthopedic, College of Clinical Medicine, Yangzhou University, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, China (mainland))
Med Sci Monit 2018; 24:5874-5880
Osteosarcoma is a prevalent type of bone tumor mainly reported in children and adolescents. The treatments for osteosarcoma are limited and are associated with serious adverse effects. In this study we evaluated the anticancer activity of Evodiamine, a plant-derived natural product, against a panel of osteosarcoma cells and explored the underlying mechanisms.
MATERIAL AND METHODS: The viability of osteosarcoma cell lines was investigated by MTT assay. Apoptosis was detected by DAPI and annexin V/PI staining and cell cycle analysis was performed by flow cytometry. The expression of the proteins was examined by Western blotting.
RESULTS: The results of the present study indicated that Evodiamine inhibited the proliferation of U2OS osteosarcoma cells with an IC50 of 6 µM. Further investigations indicated the antiproliferative effects of Evodiamine are due to induction of apoptosis and G2/M cell cycle arrest. The results of Western blotting revealed that the expression of several apoptosis (Cytochrome c, Bax, Bid, Caspase 3, 9, 8, and PARP) and cell cycle-related proteins (cyclin B1, Cdc25c, and Cdc2) was significantly altered. Evodiamine also suppressed the migration and invasion of U2OS osteosarcoma cells. Moreover, Evodiamine downregulated the expression of important regulatory proteins such as p-MEK and p-ERK, leading to the inhibition of Raf/MEK/ERK signalling pathways.
CONCLUSIONS: We found that Evodiamine exerts anticancer effects on osteosarcoma cells and has potential in the treatment of osteosarcoma.
Keywords: Apoptosis, Cell Cycle, Osteosarcoma