Titre du document / Document title

Depsipeptide (FK228) inhibits growth of human prostate cancer cells

Auteur(s) / Author(s)

LAI Ming-Tsung ^{(1 2)} ; YANG Chuan-Ching ⁽¹⁾ ; LIN Tsai-Yun ⁽¹⁾ ; TSAI Fuu-Jen ^{(3 4)} ; CHEN Wen-Chi ^{(3 5 6)} ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Life Science, National Tsing Hua University, Hsinchu, TAIWAN, PROVINCE DE CHINE
⁽²⁾ Department of Pathology, College of Medicine, China Medical University, Taichung, TAIWAN, PROVINCE DE CHINE
⁽³⁾ College of Chinese Medicine, China Medical University, Taichung, TAIWAN, PROVINCE DE CHINE
⁽⁴⁾ Asia University, Taichung, TAIWAN, PROVINCE DE CHINE
⁽⁵⁾ Graduate Institute of Integrated Medicine, China Medical University, Taichung, TAIWAN, PROVINCE DE CHINE
⁽⁶⁾ Department of Urology, China Medical University Hospital, Taichung, TAIWAN, PROVINCE DE CHINE

Résumé / Abstract

FK228 (depsipeptide) is a natural prodrug that inhibits class I histone deacetylases. We aimed to investigate the effects FK228 has on prostate cancer cells in vivo. In non-obese diabetic-severe combined immunodeficient mice implanted with human prostate cancer cells, 50 mg/kg FK228 given orally 3 times a week inhibited tumor growth and metastasis. The median time to the experimental end point (tumor volume 2 cm³ or death) in the untreated group was 52 days, and average tumor volume was 0.8 ±0.18 cm³. At the same time, 94.4% of FK228-treated mice survived and had average tumor volumes of 0.37 ±0.1 cm³. All untreated animals died at 98 days, whereas, 61% of treated animal remained alive. Sizeable metastatic tumors positively stained for prostate-specific antigen (PSA), and limited air gaps were found in the lungs of untreated mice. In animals treated with FK228, lung morphology appeared normal. Primary tumors of treated animals were highly positive for PSA, and had an increased level of p21 and the proapoptotic protein Bax. Sections taken from FK228-treated animals and examined under an electron microscope showed condensed chromatin and apoptotic bodies. PSA serum levels were higher in untreated than in treated animals and correlated with tumor volume. Because prolonged oral administration of 50 mg/kg or a single oral dose of 1.2 g/kg FK228 did not cause adverse effects and inhibited proliferation of human prostate cancer cells in vivo, FK228 likely has a potential anticancer effect for prostate cancer.

Revue / Journal Title

Urologic oncology   ISSN 1078-1439 

Source / Source

2008, vol. 26, n^o2, pp. 182-189 [8 page(s) (article)] (14 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier Science, New York, NY, ETATS-UNIS  (1995) (Revue)

Mots-clés anglais / English Keywords

Lung disease ; Respiratory disease ; Prostate disease ; Cancer ; Malignant tumor ; Urinary system disease ; Male genital diseases ; Lung metastasis ; Urology ; Nephrology ; Cancerology ; Prodrug ; Prostate specific antigen ; Tumoral marker ; Tumor cell ; Human ; Growth ; Histone deacetylase inhibitor ; Prostate adenocarcinoma ; Antineoplastic agent ; Depsipeptide ; Prostate cancer ;

Mots-clés français / French Keywords

Pathologie des poumons ; Pathologie de l'appareil respiratoire ; Pathologie de la prostate ; Cancer ; Tumeur maligne ; Pathologie de l'appareil urinaire ; Pathologie de l'appareil génital mâle ; Métastase pulmonaire ; Urologie ; Néphrologie ; Cancérologie ; Promédicament ; Antigène spécifique prostate ; Marqueur tumoral ; Cellule tumorale ; Homme ; Croissance ; Inhibiteur histone deacetylase ; Adénocarcinome de la prostate ; Anticancéreux ; Depsipeptide ; Cancer de la prostate ;

Mots-clés espagnols / Spanish Keywords

Pulmón patología ; Aparato respiratorio patología ; Prostata patología ; Cáncer ; Tumor maligno ; Aparato urinario patología ; Aparato genital macho patología ; Metástasis pulmonar ; Urología ; Nefrología ; Cancerología ; Promedicamento ; Antigeno específico prostata ; Marcador tumoral ; Célula tumoral ; Hombre ; Crecimiento ; Inhibidor histone deacetylase ; Adenocarcinoma próstata ; Anticanceroso ; Depsipéptido ; Cáncer de la próstata ;

Mots-clés d'auteur / Author Keywords

FK228 ; Histone deacetylase inhibitor ; Prostate-specific antigen ; Prodrug ; Lung metastasis ; Prostate adenocarcinoma ;

Localisation / Location

INIST-CNRS, Cote INIST : 20819, 35400017363566.0120