Magnolol suppresses vascular endothelial growth factor-induced angiogenesis by inhibiting Ras-dependent mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signaling pathways.

Abstract

Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, has been reported to possess anticancer activity. Recent studies have also demonstrated that magnolol inhibits cell growth and induces the apoptosis of cancer cells. However, the effects of magnolol on vascular endothelial growth factor (VEGF)-induced angiogenesis in endothelial cells have not been studied. In the present study, we have used human umbilical vein endothelial cells (HUVECs) to investigate the antiangiogenic effect and molecular mechanism of magnolol. Magnolol inhibited the VEGF-induced proliferation, chemotactic motility and tube formation of HUVECs in vitro as well as the vessel sprouting of the aorta ex vivo. Furthermore, magnolol inhibited VEGF-induced Ras activation and subsequently suppressed extracellular signal-regulated kinase (ERK), phosphatidylinositol-3-kinase (PI3K)/Akt and p38, but not Src and focal adhesion kinase (FAK). Interestingly, the knockdown of Ras by short interfering RNA produced inhibitory effects that were similar to the effects of magnolol on VEGF-induced angiogenic signaling events, such as ERK and Akt/eNOS activation, and resulted in the inhibition of proliferation, migration, and vessel sprouting in HUVECs. In combination, these results demonstrate that magnolol is an inhibitor of angiogenesis and suggest that this compound could be a potential candidate in the treatment of angiogenesis-related diseases.

• Authors: Ki Mo Kim, No Soo Kim, Jinhee Kim, Jong-Shik Park, Jin Mu Yi, Jun Lee, Ok-Sun Bang
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 65 Issue 8 Pg. 1245-53 ( 2013) ISSN: 1532-7914 [Electronic] United States
• PMID: 24066970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents, Phytogenic
• Biphenyl Compounds
• Lignans
• Plant Extracts
• Vascular Endothelial Growth Factors
• magnolol
• NOS3 protein, human
• Nitric Oxide Synthase Type III
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Biphenyl Compounds (pharmacology)
• Cell Proliferation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (genetics, metabolism)
• Human Umbilical Vein Endothelial Cells
• Humans
• Lignans (pharmacology)
• Magnolia (chemistry)
• Male
• Neovascularization, Pathologic (drug therapy)
• Nitric Oxide Synthase Type III (genetics, metabolism)
• Phosphatidylinositol 3-Kinase (genetics, metabolism)
• Plant Extracts (pharmacology)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Vascular Endothelial Growth Factors (metabolism)