Abstract
Glioma is the foremost recurrent type of brain tumor in humans;in particular, glioblastoma (GBM) is the main formof brain tumor(GBM)that is highly proliferative and impervious to apoptosis. Triphlorethol-A (TA),a phlorotanninisolated from Ecklonia cava, exhibited cytoprotective, antioxidant, and anticancer properties. However, the exact molecular action of TA in the U251 human GBM cells remains unknown. This may be the first report on the antiproliferative and apoptotic mechanisms of TA on GBM. The cytotoxicity, intracellular reactive oxygen species (ROS), matrix metalloproteinase(MMP), and cell apoptosis activity of TA havebeen evaluated by theMTT assayand byDCFH-DA, Rh-123, AO/EB, and western blot analysis. Theresults obtained showed that TA abridged the viability of U251 cells, whileMMP increased apoptosis by increasing theROS levels in a time-dependent manner. The results showed that a reduction in U251 cellproliferation wasassociated with the regulation of JAK2/STAT3 and p38 MAPK/ERK signaling pathways. TA was found tosuppresspJAK, pSTAT3, p38 MAPK, and pERK phosphorylation, therebycausing Bax/Bcl-2 imbalance, activatingthe caspase cascadeand cytochromec, and inducingapoptosis. Our findings showed that the suppression of JAK2/STAT3 and p38 MAPK/ERK signaling by TA results in cell growth arrest and stimulation of apoptosis in GBM cells. These studies justify the protective remedy of TA against GBM.
Published Version
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