Dykellic Acid Inhibits Cell Migration and Tube Formation by RhoA-GTP Expression

Dykellic acid, a novel factor initially identified from the culture broth of Westerdykella multispora F50733, has been shown to inhibit matrix metalloprotease 9 activity, caspase-3 activity, B cell proliferation and LPS-induced IgM production, suggesting that this factor may have anti-cancer effects...

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Bibliographic Details
Published in:Biological & Pharmaceutical Bulletin 2006, Vol.29(11), pp.2256-2259
Main Authors: Heo, Jin-Chul, Park, Ja-Young, Woo, Sang-Uk, Rho, Jae-Rang, Lee, Ho-Jae, Kim, Sung-Uk, Kho, Yung-Hee, Lee, Sang-Han
Format: Article
Language:English
Subjects:
angiogenesis
Animals
Blood Vessels - drug effects
Blood Vessels - physiology
Blotting, Western
Cell Line
Cell Line, Tumor
cell migration
Cell Movement - drug effects
Cell Proliferation - drug effects
Dose-Response Relationship, Drug
dykellic acid
Endothelial Cells - drug effects
Endothelial Cells - physiology
Humans
invasion
Mice
Neoplasm Invasiveness - prevention & control
Neovascularization, Pathologic - metabolism
Neovascularization, Pathologic - prevention & control
Propionates - chemistry
Propionates - pharmacology
Pyrones - chemistry
Pyrones - pharmacology
RhoA
rhoA GTP-Binding Protein - metabolism
RhoA-GTP
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Summary:Dykellic acid, a novel factor initially identified from the culture broth of Westerdykella multispora F50733, has been shown to inhibit matrix metalloprotease 9 activity, caspase-3 activity, B cell proliferation and LPS-induced IgM production, suggesting that this factor may have anti-cancer effects. In an effort to further address the possible anti-tumoral effects of dykellic acid, we used wound healing, invasion and RhoA-GTP assays to examine the effects of dykellic acid on cell migration, invasion and angiogenesis. Our results revealed that dykellic acid dose-dependently inhibits B16 cell migration and motility, and inhibits HUVEC tube formation. Western blot analysis of the active form of RhoA (RhoA-GTP) showed that dykellic acid treatment decreased the levels of RhoA-GTP. These findings collectively suggest that dykellic acid may have both anti-metastatic and anti-angiogenic acitivites, and provides the first evidence for the involvement of RhoA in dykellic acid-induced effects.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.29.2256