Methyl gallate isolated from Mangifera pajang kernel induces proliferation inhibition and apoptosis in MCF-7 breast cancer cells via oxidative stress

Objective:To determine the lead bioactive compound in kernel extract of Mangifera pajang and its anti-cancer activity against human breast cancer cell lines with positive estrogen receptor(MCF-7).Methods:The methanolic extract of dried powder kernel of Mangifera pajang was exposed to column chromatography for isolation.The structural elucidation of the isolated compound was characterized using infrared,nuclear magnetic resonance,mass spectrometry.Furthermore,cytotoxicity,morphological changes,flow cytometry and cell cycle arrest analyses were performed to examine the mechanism of anti-proliferation and apoptosis induced by methyl gallate against MCF-7.Results:One compound was isolated from the methanolic extract of Mangifera pajang kernel and identified as methyl gallate.The flow cytometric results demonstrated induction of apoptosis in MCF-7 cells by three concentrations of methyl gallate.The cell cycle arrest showed a significant(P<0.05)decrease in cell progression at G2/M phase of MCF-7 after treatment with 100μM of methyl gallate.The cell percentage of early and late apoptosis was significant at 10 and 100μM of methyl gallate.Also,methyl gallate treatment induced up-regulation of reactive oxygen species levels in MCF-7 cells with a reduction in superoxide dismutase levels.Conclusions:These findings indicate that isolated methyl gallate from Mangifera pajang kernel extracts induces growth inhibition and apoptosis in MCF-7 cells via up-regulating oxidative stress pathway.

The antioxidant methyl gallate inhibits fungal growth and deoxynivalenol production in Fusarium graminearum

Production of the Fusarium toxin deoxynivalenol(DON)is associated with oxidative stress and has been indicated to be part of an adaptive response to oxidative stress in the important wheat fungus Fusarium graminearum.In this study,we found that the antioxidant methyl gallate(MG)displays inhibitory effects against mycelial growth,conidial formation and germination,and DON biosynthesis in F.graminearum in a dose-dependent manner.Treatment with 0.05%(w/v)MG resulted in an abnormal swollen conidial morphology.The expression of the TRI genes involved in DON biosynthesis was significantly reduced,and the induction of Tri1-GFP green fluorescence signals in the spherical and crescent-shaped toxisomes was abolished in the MG-treated mycelium.RNA-Seq analysis of MG-treated F.graminearum showed that 0.5%(w/v)MG inhibited DON production by possibly altering membrane functions and oxidoreductase activities.Coupled with the observations that MG treatment decreases catalase,POD and SOD activity in F.graminearum.The results of this study indicated that MG displays antifungal activity against DON production by modulating its oxidative response.Taken together,the current study revealed the potential of MG in inhibiting mycotoxins in F.graminearum.