Identification of apoptotic and antiangiogenic activities of terazosin in human prostate cancer and endothelial cells
Journal
Journal of Urology
Journal Volume
169
Journal Issue
2
Pages
724-729
Date Issued
2003
Author(s)
Abstract
Purpose: It has been suggested that terazosin has an inhibitory effect on prostate tumor growth. We determined if terazosin action contributes to direct suppression of the angiogenic effect. Materials and Methods: PC-3 cells and primary cultures of human benign prostatic cells were used in this study. The cytotoxic effect was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase release reaction. The in vivo angiogenic effect was determined in nude mice models, followed by histological examination and quantification by the hemoglobin detection assay. In vitro determination of cell migration, proliferation and tube formation was performed in cultured human umbilical vein endothelial cells. Results: Terazosin induced cytotoxicity in PC-3 and human benign prostatic cells with an IC50 of more than 100 μM. The positive terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling and lactate dehydrogenase release reaction was associated with terazosin induced cytotoxicity, indicating apoptotic and necrotic cell death. Furthermore, cytotoxicity due to terazosin action was not a common characteristic of a quinazoline based structure. Terazosin significantly inhibited vascular endothelial growth factor induced angiogenesis in nude mice with an IC50 of 7.9 μM., showing that it had a more potent anti-angiogenic than cytotoxic effect. Terazosin also effectively inhibited vascular endothelial growth factor induced proliferation and tube formation in cultured human umbilical vein endothelial cells (IC50 9.9 and 6.8 μM., respectively). Conclusions: Together our data suggest that terazosin shows direct anti-angiogenic activity through the inhibition of proliferation and tube formation in endothelial cells. This action may partly explain the in vivo antitumor potential of terazosin.
SDGs
Other Subjects
2 [4 [4 (2 methoxyphenyl)piperazinyl]butyl]amino 4 cyclohexylaminoquinazolin; 4 [3 [4 (2 methoxyphenyl)piperazinyl]propyl]aminoquinazolin 2 carboxamide; alpha 1 adrenergic receptor blocking agent; angiogenesis inhibitor; ethyl 4 [3 [4 (2 methoxyphenyl)piperazinyl]aminoquinazolin 2 carboxylate]; ew 154; ew 65; fh 71; lactate dehydrogenase; quinazoline derivative; terazosin; thymidine; tritium; unclassified drug; vasculotropin; angiogenesis; animal model; apoptosis; article; cancer cell; cell migration; controlled study; drug cytotoxicity; drug structure; endothelium cell; human; human cell; male; mouse; nonhuman; nude mouse; priority journal; prostate adenocarcinoma; prostate carcinoma
Type
journal article