The anticancer prodrugs of butyric acid AN-7 and AN-9, possess antiangiogenic properties.
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.
Blank-Porat
Diana
D
Felsenstein Center for Medical Research, Tel Aviv University Beilinson Campus, Petach Tikva 49100, Israel.
Gruss-Fischer
Tal
T
Tarasenko
Nataly
N
Malik
Zvi
Z
Nudelman
Abraham
A
Rephaeli
Ada
A
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011355:Prodrugs / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D002087:Butyrates; D016222:Fibroblast Growth Factor 2; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D009943:Organophosphorus Compounds; D051059:PTEN Phosphohydrolase; D011355:Prodrugs; D018719:Erb-b2 Receptor Tyrosine Kinases; C497443:Hif1a protein, mouse; C502471:diethoxyphosphoryloxymethyl butanoate; C070441:pivalyloxymethyl butyrate; C487757:Pten protein, mouse