Identification of apoptotic and antiangiogenic activities of terazosin in human prostate cancer and endothelial cells

Shiow Lin Pan, Jih Hwa Guh, Ying Wen Huang, Ji Wang Chern, Jui Yi Chou, Che Ming Teng

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)724-729
Number of pages6
JournalJournal of Urology
Volume169
Issue number2
DOIs
Publication statusPublished - Feb 1 2003
Externally publishedYes

Fingerprint

Terazosin
Prostatic Neoplasms
Endothelial Cells
Inhibitory Concentration 50
Human Umbilical Vein Endothelial Cells
L-Lactate Dehydrogenase
Nude Mice
Vascular Endothelial Growth Factor A
Quinazolines
Primary Cell Culture
DNA Nucleotidylexotransferase

Keywords

  • Apoptosis
  • Endothelium
  • Prostate
  • Prostatic neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

Identification of apoptotic and antiangiogenic activities of terazosin in human prostate cancer and endothelial cells. / Pan, Shiow Lin; Guh, Jih Hwa; Huang, Ying Wen; Chern, Ji Wang; Chou, Jui Yi; Teng, Che Ming.

In: Journal of Urology, Vol. 169, No. 2, 01.02.2003, p. 724-729.

Research output: Contribution to journalArticle

Pan, Shiow Lin ; Guh, Jih Hwa ; Huang, Ying Wen ; Chern, Ji Wang ; Chou, Jui Yi ; Teng, Che Ming. / Identification of apoptotic and antiangiogenic activities of terazosin in human prostate cancer and endothelial cells. In: Journal of Urology. 2003 ; Vol. 169, No. 2. pp. 724-729.
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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.",
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AU - Guh, Jih Hwa

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AU - Chern, Ji Wang

AU - Chou, Jui Yi

AU - Teng, Che Ming

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N2 - 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.

AB - 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.

KW - Apoptosis

KW - Endothelium

KW - Prostate

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