Down regulation of matrix metalloproteinases by spearmint extract in Wehi-164 cells

Abstract

Tumor invasion and metastasis are the main causes of cancer death. Matrix metalloproteinases (MMPs) are endopeptidases which degredate the extracellular matrix proteins. MMPs have an important role in tumor progression and metastasis. Fibrosarcoma has been recognized as a highly metastatic cancer which its current therapeutic methods have not been very successful. Medicinal plants are widely used in treatment of cancers. Spearmint is a herb with well known anti-tumor activities. In the present study, the effect of hydro extract of spearmint on MMP-2/9 activities in Wehi-164 fibrosarcoma cells has been evaluated in vitro. Wehi-164 cells were cultured in Roswell Park Memorial Institute (RPMI) medium with 10% fetal bovine serum (FBS). Then the cells at logarithmic growth phase were incubated with different concentrations of hydro extract of spearmint (0.1 to 10 mg/ml) in the presence or absence of phorbol myristate acetate (PMA) (25 ng/ml) for 24, 48 and 72 h. The MMP-2/MMP-9 activity in conditioned medium was evaluated by gelatin zymography. Spearmint aqueous extract significantly reduced the MMP-2 and PMA-induced MMP-9 activity in fibrosarcoma Wehi-164 cells dose dependently. The aqueous extract of spearmint showed inhibitory effect on MMP-2/MMP-9 activity in Wehi-164 fibrosarcoma cells. So, the anti-tumor effects of spearmint may be in part due to its inhibitory effects on MMP-2/MMP-9 activity. Evaluation of effective component (s) in the spearmint extract with anti-MMP activity and their mechanism of action could be useful in designing novel natural MMP inhibitors.

The Wonderful Activities of the Genus Mentha: Not Only Antioxidant Properties

“…Hep2 cells showed less sensitivity than the other two cell lines [ 150 ]. Differently, aqueous extract of M. spicata showed cytotoxicity effect on U937 leukemia cells (IC 50 = 4.8 mg/mL) [ 151 ]. The methanolic extract of M. longifolia at a concentration >0.5 µg/µl demonstrated antiproliferative effects in adrenocortical tumor cell lines, with modulating activity on MAPK and PI3k/Akt pathways [ 152 ].…”

“…Mentha species exhibited modulatory effects on the expression or activity of some MMPs, and Liu et al reported that 10, 30, and 100 mg/kg of spearmint oil significantly decreased the expression of TNF-α, IL-1β, and MMP-9 in rat lung tissues [ 180 ]. Moreover, treatment of Wehi-164 fibrosarcoma cells with aqueous extract of spearmint led to significant reduction in MMP-2/MMP-9 activity in a dose-dependent manner, as there was no detectable activity of MMP-2/MMP-9 in Wehi-164 cells treated with 10 mg/mL of the extract after 24, 48, and 72 h [ 151 ]. A phytomics analysis (analysis of primary and secondary metabolites of plant extracts) showed that 500 µg/mL of M. piperita extract had significant inhibitory effect on the activity of MMP-1 (84.4%), MMP-8 (80.46%), MMP-13 (91.02%) [ 181 ].…”