Abstract
The antiangiogenic and antineoplastic activities of the butyric acid prodrugs AN-7 and AN-9 were demonstrated in vitro with HUVEC by inhibition of proliferation and vascular tubes formation, enhanced apoptosis, and inhibition of 22Rv-1 cells migration. In the sc implanted human prostate tumors (22Rv-1) in nude mice, AN-7 significantly inhibited Ki-67, HIF-1alpha, HER-2/neu, bFGF and increased PTEN level. AN-7 and AN-9 reduced hemoglobin accumulation in matrigel plugs implanted sc in Balb-c mice. Herein, we show that the anticancer activity of AN-7 and AN-9 can be attributed in part to their antiangiogenic activities suggesting potential therapeutic benefits for prostate cancer patients.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Butyrates / pharmacology*
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Cell Proliferation / drug effects
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Endothelium, Vascular / drug effects
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Fibroblast Growth Factor 2 / genetics
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Fibroblast Growth Factor 2 / metabolism
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Ki-67 Antigen / genetics
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Ki-67 Antigen / metabolism
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neovascularization, Pathologic / drug therapy*
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Organophosphorus Compounds / pharmacology*
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / metabolism
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Prodrugs / pharmacology*
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Prostatic Neoplasms / drug therapy
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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Receptor, ErbB-2 / genetics
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Receptor, ErbB-2 / metabolism
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Tumor Cells, Cultured
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Umbilical Veins / cytology
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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Butyrates
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Hif1a protein, mouse
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Hypoxia-Inducible Factor 1, alpha Subunit
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Ki-67 Antigen
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Organophosphorus Compounds
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Prodrugs
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diethoxyphosphoryloxymethyl butanoate
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Fibroblast Growth Factor 2
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pivalyloxymethyl butyrate
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Receptor, ErbB-2
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PTEN Phosphohydrolase
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Pten protein, mouse