Honokiol Inhibits Tumor Necrosis Factor-α-Stimulated Rat Aortic Smooth Muscle Cell Proliferation via Caspase- and Mitochondrial-Dependent Apoptosis

• Published in: Inflammation 2014-02, Vol.37 (1), p.17-26
• Main Authors: Fan, Shuli, Li, Xu, Lin, Jie, Chen, Sijiao, Shan, Jinhua, Qi, Guoxian
• Format: Article
• Language: English
• Subjects: Animals; Aorta; Aorta - metabolism; Apoptosis; Apoptosis - drug effects; Bax protein; Bcl-2 protein; bcl-2-Associated X Protein - biosynthesis; Biomedicine; Biphenyl Compounds - pharmacology; c-Jun protein; Cardiovascular diseases; Caspase; Caspases - metabolism; Cell cycle; Cell proliferation; Cell Proliferation - drug effects; Cell Survival; Cells, Cultured; Cyclin D1; Cyclin D1 - biosynthesis; Cyclin E; Cyclin E - biosynthesis; Cyclin-Dependent Kinase 2 - biosynthesis; Cyclin-dependent kinase 4; Cyclin-Dependent Kinase 4 - biosynthesis; Cyclin-dependent kinases; Cytochrome c; Cytochromes c - secretion; Cytosol; Drugs, Chinese Herbal - pharmacology; Enzyme Inhibitors - pharmacology; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; G1 Phase Cell Cycle Checkpoints - drug effects; Immunology; Internal Medicine; JNK Mitogen-Activated Protein Kinases - metabolism; JNK protein; Kinases; Lignans - pharmacology; Male; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - metabolism; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Pathology; Pharmacology/Toxicology; Phosphorylation; Phosphorylation - drug effects; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Rats; Rats, Sprague-Dawley; Rheumatology; Signal Transduction; Smooth muscle; Transcription factors; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-013-9707-y

ABSTRACT This study aims to investigate the effects of honokiol on proliferation, cell cycle, and apoptosis in tumor necrosis factor (TNF)-α-induced rat aortic smooth muscle cells (RASMCs). We found that honokiol treatment showed potent inhibitory effects on TNF-α-induced RASMC proliferation, which were associated with G0/G1 cell cycle arrest and downregulation of cell cycle-related proteins, including cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2 and CDK4. Furthermore, honokiol treatment led to the release of cytochrome c into cytosol and a loss of mitochondrial membrane potential (ΔΨm), as well as a decrease in the expression of Bcl-2 and an increase in the expression of Bax. Treatment with honokiol also reduced TNF-α-induced phosphorylation of p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase. Taken together, our results suggest that honokiol suppresses TNF-α-stimulated RASMC proliferation via caspase- and mitochondria-dependent apoptosis and highlight the therapeutic potential of honokiol in the prevention of cardiovascular diseases.