Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo - PubMed (original) (raw)

. 2000 Sep 15;60(18):5165-70.

Affiliations

PMID: 11016644

Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo

L M Butler et al. Cancer Res. 2000.

Abstract

Suberoylanilide hydroxamic acid (SAHA) is the prototype of a family of hybrid polar compounds that induce growth arrest in transformed cells and show promise for the treatment of cancer. SAHA induces differentiation and/or apoptosis in certain transformed cells in culture and is a potent inhibitor of histone deacetylases. In this study, we examined the effects of SAHA on the growth of human prostate cancer cells in culture and on the growth of the CWR22 human prostate xenograft in nude mice. SAHA suppressed the growth of the LNCaP, PC-3, and TSU-Pr1 cell lines at micromolar concentrations (2.5-7.5 microM). SAHA induced dose-dependent cell death in the LNCaP cells. In mice with transplanted CWR222 human prostate tumors, SAHA (25, 50, and 100 mg/kg/day) caused significant suppression of tumor growth compared with mice receiving vehicle alone; treatment with 50 mg/kg/day resulted in a 97% reduction in the mean final tumor volume compared with controls. At this dose, there was no detectable toxicity as evaluated by weight gain and necropsy examination. Increased accumulation of acetylated core histones was detected in the CWR22 tumors within 6 h of SAHA administration. SAHA induced prostate-specific antigen mRNA expression in CWR22 prostate cancer cells, resulting in higher levels of serum prostate-specific antigen than predicted from tumor volume alone. The results suggest that hydroxamic acid-based hybrid polar compounds inhibit prostate cancer cell growth and may be useful, relatively nontoxic agents for the treatment of prostate carcinoma.

PubMed Disclaimer

Cited by

Modulation of Abundance and Location of High-Mobility Group Box 1 in Human Microglia and Macrophages under Oxygen-Glucose Deprivation.
Bielawski PB, Zhang I, Correa-Paz C, Campos F, Migliavacca M, Polo E, Del Pino P, Pelaz B, Vivien D, Maysinger D. Bielawski PB, et al. ACS Pharmacol Transl Sci. 2024 Feb 27;7(3):680-692. doi: 10.1021/acsptsci.3c00271. eCollection 2024 Mar 8. ACS Pharmacol Transl Sci. 2024. PMID: 38481701
Pan-histone deacetylase inhibitor vorinostat suppresses osteoclastic bone resorption through modulation of RANKL-evoked signaling and ameliorates ovariectomy-induced bone loss.
Peng X, Wang T, Wang Q, Zhao Y, Xu H, Yang H, Gu Y, Tao Y, Yan B, Xu Y, Geng D. Peng X, et al. Cell Commun Signal. 2024 Mar 4;22(1):160. doi: 10.1186/s12964-024-01525-w. Cell Commun Signal. 2024. PMID: 38439009 Free PMC article.
Epigenetic (De)regulation in Prostate Cancer.
Xu C, Zhao S, Cai L. Xu C, et al. Cancer Treat Res. 2023;190:321-360. doi: 10.1007/978-3-031-45654-1_10. Cancer Treat Res. 2023. PMID: 38113006
Identification of druggable genes for multiple myeloma based on genomic information.
Satria RD, Irham LM, Adikusuma W, Puspitaningrum AN, Afief AR, Khair RE, Septama AW. Satria RD, et al. Genomics Inform. 2023 Sep;21(3):e31. doi: 10.5808/gi.23011. Epub 2023 Sep 27. Genomics Inform. 2023. PMID: 37813627 Free PMC article.
A multiplexed, single-cell sequencing screen identifies compounds that increase neurogenic reprogramming of murine Muller glia.
Tresenrider A, Hooper M, Todd L, Kierney F, Blasdel N, Trapnell C, Reh TA. Tresenrider A, et al. bioRxiv [Preprint]. 2024 Apr 12:2023.09.26.559569. doi: 10.1101/2023.09.26.559569. bioRxiv. 2024. PMID: 37808650 Free PMC article. Preprint.

Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo - PubMed (original) (raw)