Momordica cochinchinensis Suppresses the Human Breast Cancer Cells Growth and Migration by Inhibiting Mevalonate Pathway

Background: Momordica cochinchinensis (MC) is shown with high antioxidation and is used as herbal medicine in South-East countries. Objectives: This study aims to determine the four parts (aril, fruit, leaf, and seed) of MC extract against human breast cancer cells with underlying mechanisms of actions. Materials and Methods: The effects of MC extract were examined by sulforhodamine B, colony formation, wound healing, real time polymerase chain reaction (RT-PCR), and Western blotting method. Results: Four parts of MC extracts significantly increased MCF-7 cells death, interestingly, seed extract had the greatest activity with IC50 values of 412.3 +/- 49.8 mu g/mL for 24 h and 113.3 +/- 6.4 mu g/mL for 48 h. MC extracts potentiated the anticancer drug effect, doxorubicin, with lower IC50 values when compared with MC treatment alone. Moreover, MC extracts decreased colony formation and accompanied by inhibited cell migration. Furthermore, Seed extract inhibited migration by reducing matrix metalloproteinases (MMP) 2, MMP 9, and vascular endothelial growth factor A (VEGFA) inhibition. The molecular analyses revealed that seed extract inhibited cell viability by decreasing cyclin D1 consistent with activating p21, cytochrome c, and caspase-3 protein levels along with reduction of mevalonate (MVA) pathway, Rac1, and RhoA levels, it appeared to inhibit growth and migration. Conclusion: Taken together, MC extract induces MCF-7 cell death and decreases cell migration relatively via attenuation of MVA pathway.