Litebamine, a phenanthrene alkaloid from the wood of Litsea cubeba, inhibits rat smooth muscle cell adhesion and migration on collagen

Chi Hung Huang, Wei Jan Huang, Su Jane Wang, Pi Hui Wu, Wen Bin Wu

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Smooth muscle cells (SMCs) play an important role in the development of atherosclerosis and restenosis after angioplasty and coronary bypass grafting. The pathogenesis of these vascular diseases includes the abnormal production of extracellular matrix (ECM) proteins by SMCs and their interactions with this newly synthesized and preexisting ECM. Litebamine, a natural phenanthrene alkaloid from the wood of Litsea cubeba, has been shown to inhibit platelet aggregation and thromboxane B2 formation, suggesting its antithrombotic activity. In the present study we examined litebamine effects on vascular SMC adhesion and migration. Our results indicated that litebamine inhibited rat aortic SMCs (RASMCs) and A10 thoracic SMCs adhesion to collagen but not to other matrix proteins, suggesting its specificity on collagen. This inhibition was possibly resulted from that litebamine attenuated immobilized collagen-induced focal adhesion kinase (FAK) phosphorylation and actin cytoskeleton reorganization in RASMCs, as determined by Western blotting and immunofluorescence microscopy. In a functional study, litebamine also inhibited platelet-derived growth factor (PDGF)-induced RASMC migration but did not affect PDGF-induced matrix metalloproteinases (MMPs) secretion. Strikingly, among the tested kinases involved in PDGF-induced migration, only PDGF-induced phosphatidylinositol-3 kinase (PI-3K) activation was inhibited by litebamine. Taken together, we demonstrated here that litebamine can functionally inhibit vascular SMC adhesion and migration and elucidated its possible mechanisms of action. As SMC adhesion and migration are critical events in disease-related vascular remodeling, this compound may have beneficial effects in preventing cardiovascular diseases.

Original languageEnglish
Pages (from-to)25-31
Number of pages7
JournalEuropean Journal of Pharmacology
Volume596
Issue number1-3
DOIs
Publication statusPublished - Oct 31 2008

Fingerprint

Litsea
Alkaloids
Cell Adhesion
Smooth Muscle Myocytes
Cell Movement
Collagen
Platelet-Derived Growth Factor
Vascular Smooth Muscle
Phosphatidylinositol 3-Kinase
Focal Adhesion Protein-Tyrosine Kinases
Thromboxane B2
Extracellular Matrix Proteins
antineoplaston A10
litebamine
phenanthrene
Matrix Metalloproteinases
Actin Cytoskeleton
Vascular Diseases
Platelet Aggregation
Angioplasty

Keywords

  • Adhesion
  • Alkaloid
  • Cardiovascular disease
  • Litebamine
  • Migration
  • Natural compound
  • PDGF
  • Smooth muscle cell

ASJC Scopus subject areas

  • Pharmacology

Cite this

Litebamine, a phenanthrene alkaloid from the wood of Litsea cubeba, inhibits rat smooth muscle cell adhesion and migration on collagen. / Huang, Chi Hung; Huang, Wei Jan; Wang, Su Jane; Wu, Pi Hui; Wu, Wen Bin.

In: European Journal of Pharmacology, Vol. 596, No. 1-3, 31.10.2008, p. 25-31.

Research output: Contribution to journalArticle

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abstract = "Smooth muscle cells (SMCs) play an important role in the development of atherosclerosis and restenosis after angioplasty and coronary bypass grafting. The pathogenesis of these vascular diseases includes the abnormal production of extracellular matrix (ECM) proteins by SMCs and their interactions with this newly synthesized and preexisting ECM. Litebamine, a natural phenanthrene alkaloid from the wood of Litsea cubeba, has been shown to inhibit platelet aggregation and thromboxane B2 formation, suggesting its antithrombotic activity. In the present study we examined litebamine effects on vascular SMC adhesion and migration. Our results indicated that litebamine inhibited rat aortic SMCs (RASMCs) and A10 thoracic SMCs adhesion to collagen but not to other matrix proteins, suggesting its specificity on collagen. This inhibition was possibly resulted from that litebamine attenuated immobilized collagen-induced focal adhesion kinase (FAK) phosphorylation and actin cytoskeleton reorganization in RASMCs, as determined by Western blotting and immunofluorescence microscopy. In a functional study, litebamine also inhibited platelet-derived growth factor (PDGF)-induced RASMC migration but did not affect PDGF-induced matrix metalloproteinases (MMPs) secretion. Strikingly, among the tested kinases involved in PDGF-induced migration, only PDGF-induced phosphatidylinositol-3 kinase (PI-3K) activation was inhibited by litebamine. Taken together, we demonstrated here that litebamine can functionally inhibit vascular SMC adhesion and migration and elucidated its possible mechanisms of action. As SMC adhesion and migration are critical events in disease-related vascular remodeling, this compound may have beneficial effects in preventing cardiovascular diseases.",
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