Abstract |
Arsenic compounds have been used to treat angiogenic diseases such as cancer, psoriasis, and rheumatoid arthritis in traditional oriental medicine. In recent years, arsenic trioxide ( As2O3, diarsenic oxide) has been successfully used to treat acute promyelocytic leukemia. We investigated the antiangiogenic properties of tetraarsenic oxide ( As4O6), another trivalent arsenic compound. In in vitro studies, tetraarsenic oxide inhibited the proliferation (IC50 = 99.7 nM), migration into the denuded area (IC50 = 27.4 nM), and invasion through a layer of Matrigel (IC50 = 73.5 nM) of basic fibroblast growth factor (bFGF)-stimulated bovine capillary endothelial (BCE) cells in a dose-dependent manner. Tetraarsenic oxide also inhibited the tube formation of human umbilical vein endothelial cells. Tetraarsenic oxide induced cell cycle arrest of bFGF-stimulated BCE cells in the G2/M phase and inhibited the secretion of matrix metalloproteinase-2 from BCE cells. Orally administered tetraarsenic oxide (50 mg/kg/day) inhibited bFGF-induced new-vessel formation in a rat corneal micropocket assay, and reduced by about 54% the number of experimental pulmonary metastatic nodules in mice implanted with B16F10 melanoma cells. Thus, we provide evidence that tetraarsenic oxide has effective antiangiogenic activities.
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Authors | Myung Jin Park, In Chul Park, Ill Ju Bae, Kang Moon Seo, Seung Hoon Lee, Seok Il Hong, Choong Ki Eun, Wei Zhang, Chang Hun Rhee |
Journal | International journal of oncology
(Int J Oncol)
Vol. 22
Issue 6
Pg. 1271-6
(Jun 2003)
ISSN: 1019-6439 [Print] Greece |
PMID | 12738993
(Publication Type: Journal Article)
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Chemical References |
- Angiogenesis Inhibitors
- Arsenates
- sodium arsenate
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Topics |
- Administration, Oral
- Angiogenesis Inhibitors
(pharmacology)
- Animals
- Arsenates
(administration & dosage, pharmacology)
- Capillaries
- Cattle
- Cell Cycle
(drug effects)
- Cell Movement
(drug effects)
- Cells, Cultured
- Endothelium, Vascular
(cytology, drug effects)
- Lung Neoplasms
(blood supply, drug therapy)
- Male
- Mice
- Mice, Inbred C57BL
- Neoplasm Metastasis
- Neovascularization, Pathologic
(prevention & control)
- Rats
- Rats, Sprague-Dawley
- Tumor Cells, Cultured
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