Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo.
Natural products comprise a major source of small molecular weight angiogenesis inhibitors. We have used the transformed endothelial cell line SVR as an effective screen of natural product extracts to isolate anti-angiogenesis and anti-tumor compounds. Aqueous extracts of Magnolia grandiflora exhibit potent activity in our SVR proliferation assays. We found that the small molecular weight compound honokiol is the active principle of magnolia extract. Honokiol exhibited potent anti-proliferative activity against SVR cells in vitro. In addition, honokiol demonstrated preferential inhibition of primary human endothelial cells compared with fibroblasts and this inhibition was antagonized by antibodies against TNF alpha-related apoptosis-inducing ligand. In vivo, honokiol was highly effective against angiosarcoma in nude mice. Our preclinical data suggests that honokiol is a systemically available and non-toxic inhibitor of angiogenesis and should be further evaluated as a potential chemotherapeutic agent.
Bai
Xianhe
X
Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Cerimele
Francesca
F
Ushio-Fukai
Masuko
M
Waqas
Muhammad
M
Campbell
Paul M
PM
Govindarajan
Baskaran
B
Der
Channing J
CJ
Battle
Traci
T
Frank
David A
DA
Ye
Keqiang
K
Murad
Emma
E
Dubiel
Wolfgang
W
Soff
Gerald
G
Arbiser
Jack L
JL
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000637:transplantation; D006394:Hemangiosarcoma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D017705:Lignans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D031566:Magnolia; D051379:Mice; D008819:Mice, Nude; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D000498:Allyl Compounds; D010636:Phenols
D020533:Angiogenesis Inhibitors; D001713:Biphenyl Compounds; D017705:Lignans; D010936:Plant Extracts; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols