Herbal formula HMC05 prevents human aortic smooth muscle cell migration and proliferation by inhibiting the ERK1/2 MAPK signaling cascade

Abstract

HMC05 is a formulation derived from eight medicinal herbs, and prevents neointima formation by inhibition of the mitogen-activated protein kinase (MAPK) pathway with induction of heat shock protein 27 expression. In this study, we investigated the influence of HMC05 regulation on the MAPK/extracellular signal-regulated kinase (ERK) 1/2 signaling cascade in the inhibition of the migration and proliferation of human aortic smooth muscle cells (HASMCs). The inhibitory effects of HMC05 (25, 50, and 100 μg/ml) on tumor necrosis factor-alpha (TNF-α; 0 or 100 ng/ml)-induced HASMC migration and proliferation were investigated by wound migration and proliferation assays, Western blotting and reverse transcription-polymerase chain reaction. HMC05 completely inhibited TNF-α-induced HASMC migration and proliferation. HMC05 prevented TNF-α receptor 1-mediated phosphorylation of signal transduction molecules involved in MAPK signaling cascades such as MEK1/2, ERK1/2, Elk-1 transcription factor and p90 kDa ribosomal S6 kinase. The expression of matrix metalloproteinase, a modulator of vascular smooth muscle cell proliferation and migration, was inhibited by HMCO5 treatment, as was TNF-α-induced mRNA expression of intracellular adhesion molecule 1 and vascular cell adhesion molecule 1. HMC05 disruption of the MEK/ERK/Elk-1 and p90RSK pathways prevents HASMC migration and proliferation.