Effect of Terminalia nigrovenulosa extracts and their isolated compounds on intracellular ROS generation and MMP expression in HT1080 cells

摘要

The present study evaluated the effects of Terminalia nigrovenulosa methanol extracts and their isolated compounds on intracellular reactive oxygen species (ROS) generation and matrix metalloproteinase (MMP) inhibitory activity in HT1080 cells. HT1080 cells were treated with the extracts and isolated compounds at different concentrations. Intracellular ROS generation was measured using the 2',7'-dichlorofluorescein diacetate fluorescent probe. MMP-2 and MMP-9 activities and protein expression were measured by gelatin zymography and Western blot. Luciferase activity was assessed to evaluate the effect of the extracts and compounds on activator protein-1 (AP-1) activity. The extracts of the leaves and bark of T. nigrovenulosa suppressed intracellular ROS generation and MMP-2 and MMP-9 expression in HT1080 cells. Five compounds were isolated from T. nigrovenulosa, including ellagic acid, gallic acid, catechin, ethyl gallate, and luteolin. Gallic acid decreased HT1080 cell viability at a concentration > 12.5 A mu g/mL. Luteolin, ethyl gallate, and catechin had no effect on cell viability up to 50 A mu g/mL. All isolated compounds suppressed intracellular ROS generation in a concentration-dependent manner. Moreover, ellagic acid, ethyl gallate, and luteolin reduced the MMP-2 and MMP-9 activities and protein expression in HT1080 cells. The inhibitory effects of these extracts and isolated compounds on the MMP-2 and MMP-9 activities and protein expression were related to downregulation of gene expression via suppression of the AP-1 transcription binding-factor. These findings may be useful to develop new chemotherapeutic agents for treating malignant cancers using T. nigrovenulosa extracts and the isolated compounds.