Inhibition of induced angiogenesis in a human microvascular endothelial cell line by ET-18-OCH3.
Alkyl-lysophospholipids are a group of anti-cancer compounds that have previously been shown to have the unique feature of being selectively toxic to neoplastic tissues. One of these compounds, ET-18-OCH3, has been used for purging bone marrow of cancer cells in phase I clinical trials. Tumor-induced angiogenesis has been directly correlated with tumor growth and metastasis. In this study, we examined the effect ET-18-OCH3 has on a human microvascular endothelial cell line (HMEC-1), including the following functions: angiogenesis, cell-adhesion molecule expression, and cell-junction integrity. We found that ET-18-OCH3 (in vitro) reversibly inhibited induced angiogenesis at levels that did not affect viability. At lower concentrations, ET-18-OCH3 down-regulated the expression of cell-adhesion molecules and affected the integrity of cell-to-cell junctions. This observation demonstrates this versatile family of compounds to have additional targets of action.
Candal
F J
FJ
Biological Products Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333.
Bosse
D C
DC
Vogler
W R
WR
Ades
E W
EW
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010742:Phospholipid Ethers / Q000627:therapeutic use*; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D010742:Phospholipid Ethers; C026659:edelfosine