Solvent-partitioned fractions from Ishige okamurae extract inhibit MMP-2 and MMP-9 activities in human fibrosarcoma cells in vitro

Abstract

Matrix metalloproteinases (MMPs) are endopeptidases that take significant roles in extracellular matrix degradation and therefore linked with several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Ishige okamurae, a brown alga, has been reported to possess various bioactivities including but not limited to antiviral, antimicrobial, and anti-inflammatory. In this study, the potential of I. okamurae against cancer cell invasion was evaluated through MMP inhibitory effect in HT1080 fibrosarcoma cells in vitro. I. okamurae crude extract was fractionated with organic solvents, namely water (H2O), n-butanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and n-hexane (n-Hex). The non-toxicity of fractions was confirmed by MTT assay. All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to gelatin zymography assay. Cell migration was also inhibited by 85% aq. MeOH fraction, significantly. In addition, both gene and protein expressions of MMP-2 and MMP-9, and tissue inhibitor of MMPs (TIMPs) were evaluated by RT-PCR and Western blotting, respectively. Fractions suppressed the mRNA and protein levels of MMP-2 and MMP-9 while elevating the TIMP-1 and TIMP-2, H2O fraction being the least effective while 85% aq. MeOH fraction the most. Collectively, 85% aq. MeOH fraction from brown algae could be a potential inhibitor of MMPs, suggestively considering presence of poly-unsaturated fatty acids in high amounts.