Anthraquinone derivative emodin inhibits tumor-associated angiogenesis through inhibition of extracellular signal-regulated kinase 1/2 phosphorylation.
An anthraquinone derivative, emodin, suppresses tumor development both in vitro and in vivo. In this study, we examined the anti-angiogenic activity of emodin and its modifying effect on the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. In cell cultures, emodin inhibited endothelial cell proliferation, migration, and tube formation in a dose-dependent manner. In addition, the mouse dorsal air sac assay revealed the vivo anti-angiogenic potential of emodin. Matrix metalloproteinase-9 (MMP-9) expression, which is critical for the angiogenic process, including migration and tube formation, decreased after exposure to emodin, as determined by polymerase chain reaction with reverse transcription (RT-PCR) and gelatin zymography. Moreover, the phosphorylation of ERK 1/2 decreased after exposure to emodin in a dose-dependent manner. These observations suggest that emodin has the potential to inhibit several angiogenic processes and that these effects may be related to suppression of the phosphorylation of ERK 1/2.
Kaneshiro
Tatsuya
T
Tumor Pathology, University of the Ryukyus Faculty of Medicine, 207 Uehara Nishihara-cho, Okinawa 903-0215, Japan.
Morioka
Takamitsu
T
Inamine
Morihiko
M
Kinjo
Tatsuya
T
Arakaki
Junya
J
Chiba
Itaru
I
Sunagawa
Nao
N
Suzui
Masumi
M
Yoshimi
Naoki
N
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D004642:Emodin / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008870:Microtubules / Q000187:drug effects / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020780:Matrix Metalloproteinase 9; D004642:Emodin