Emodin Induces Growth Arrest and Death of Human Vascular Smooth Muscle Cells Through Reactive Oxygen Species and p53

Abstract

Percutaneous coronary intervention is the main therapy for revascularization of occluded coronary arteries. However, a progressive artery restenosis caused by abnormal proliferation and migration of vascular smooth muscle cells (VSMC) hinders the effective treatment. In this study, we examined the effect of emodin, a natural anthraquinoid compound, on cultured VSMC. Lower doses of emodin suppressed cell proliferation and induced unscheduled DNA synthesis. Higher doses of emodin increased lumpy chromatin condensation and lysosomes in VSMC, suggesting the occurrence of apoptosis and autophagy. Emodin increased production of reactive oxygen species (ROS), which was abolished by an NADPH oxidase inhibitor diphenylene iodonium (DPI). DPI could also decrease the number of apoptosis induced by emodin, suggesting the involvement of ROS in emodin-induced apoptosis. Emodin upregulated the protein levels of p53 in a dose-dependent manner. Laser confocal microscope showed most of emodin scattering in the cytoplasms and a little within the nuclei. These findings collectively indicated that emodin induces both growth arrest and death of human VSMCs in 2 independent manners, implying it as a promising therapy for preventing restenosis.