The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade multiple components of the extracellular matrix. The significant role of MMPs in tumor invasion, neoangiogenesis and metastasis presented it as ideal pharmacological targets for cancer therapy. The effects of ursolic acid (UA) on matrix metalloproteinase (MMP) gene expression, cell invasion and cell migration were investigated MDA MB- 231 cell line.
Cytotoxicity of UA towards cancer cells was evaluated by MTT assay. MDA MB- 231 cells were cultured for 48 hrs with different concentrations (0, 5, 15 and 25μM) of UA and mRNA expressions of MMP-1, MMP-3, MMP-7, MMP-9 and MMP- 11 were analyzed by real time PCR. Cell migration wound healing assay was done at 0, 6, 24, and 48 h periods for cell migration evaluation. To asses the cell invasion MDA MB-231 cancer cells were seeded on collagen based matrigel chamber and treated with 1, 5, 10 and 15μM UA, whereas untreated cells considered as control. After48 hrs cells invaded through matrigel quantified by colorimetric method.
UA inhibited the proliferation of MDA MB -231 cells in a dose dependent manner and time dependent manner. Our results showed that UA significantly affect all MMPs except MMP-3 and 7. The expression of MMP 1, 3 and was reduced significantly 0.34, 0.11 and 0.68 fold in response to 25μM UA after 48hrs incubation in MDA MB-231 cells in comparison to control cells. Wound healing assay results exhibited that cells treated with 15μM UA significantly hindered the motility of these cells and 7.27% wound area remained unfilled after 48hrs. The cancer cells invasion was 89.75% at 25μM UA through matrigel after 48 hrs.
In conclusion, UA reduced the mRNA expressions of MMP-1, MMP-3 and MMP-9 in MDA-MB-231 cells. Ursolic acid also inhibited the invasion and migration of TNBC cells.
S. Rajoriya.
Indian Veterinary Research Institute, Bareilly U.P., India.
All authors have declared no conflicts of interest.