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  1. NTU Scholars
  2. 醫學院
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Please use this identifier to cite or link to this item: https://scholars.lib.ntu.edu.tw/handle/123456789/320587
Title: Antitumor effects of a novel phenylbutyrate-based histone deacetylase inhibitor, (S)-HDAC-42, in prostate cancer
Authors: CHING-YU CHEN 
Issue Date: 2006
Journal Volume: 12
Journal Issue: 17
Start page/Pages: 5199-5206
Source: Clinical Cancer Research 
Abstract: 
Purpose: To assess the antitumor effects of a novel phenylbutyrate-derived histone deacetylase (HDAC) inhibitor, (S)-HDAC-42, vis-?-vis suberoylanilide hydroxamic acid (SAHA) in in vitro and in vivo models of human prostate cancer. Experimental Design: The in vitro effects of (S)-HDAC-42 and SAHA were evaluated in PC-3, DU-145, or LNCaP human prostate cancer cell lines. Cell viability, apoptosis, and indicators of HDAC inhibition were assessed. Effects on Akt and members of the Bcl-2 and inhibitor of apoptosis protein families were determined by immunoblotting. Immunocompromised mice bearing established s.c. PC-3 xenograft tumors were treated orally with (S)-HDAC-42 (50 mg/kg q.o.d. or 25 mg/kg q.d.) or SAHA (50 mg/kg q.d.) for 28 days. In vivo end points included tumor volumes and intratumoral changes in histone acetylation, phospho-Akt status, and protein levels of Bcl-xL and survivin. Results: (S)-HDAC-42 was more potent than SAHA in suppressing the viability of all cell lines evaluated with submicromolar IC50 values. Relative to SAHA, (S)-HDAC-42 exhibited distinctly superior apoptogenic potency, and caused markedly greater decreases in phospho-Akt, Bcl-xL, and survivin in PC-3 cells. The growth of PC-3 tumor xenografts was suppressed by 52% and 67% after treatment with (S)-HDAC-42 at 25 and 50 mg/kg, respectively, whereas SAHA at 50 mg/kg suppressed growth by 31%. Intratumoral levels of phospho-Akt and Bcl-xL were markedly reduced in (S)-HDAC-42-treated mice, in contrast to mice treated with SAHA. Conclusions: (S)-HDAC-42 is a potent orally bioavailable inhibitor of HDAC, as well as targets regulating multiple aspects of cancer cell survival, which might have clinical value in prostate cancer chemotherapy and warrants further investigation in this regard. ? 2006 American Association for Cancer Research.
URI: http://www.scopus.com/inward/record.url?eid=2-s2.0-33749029926&partnerID=MN8TOARS
http://scholars.lib.ntu.edu.tw/handle/123456789/320587
DOI: 10.1158/1078-0432.CCR-06-0429
metadata.dc.subject.other: histone deacetylase inhibitor; protein kinase B; apoptosis; article; cell viability; drug effect; human; human cell; IC 50; priority journal; prostate cancer; xenograft
[SDGs]SDG3
Appears in Collections:醫學系

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臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

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