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Updated: Jul 14, 2026
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Antitumor activity of the histone deacetylase inhibitor MS-275 in prostate cancer models
David Z Qian1, Yong-Feng Wei, Xiaofei Wang
1The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Background:
Histone deacetylase (HDAC) inhibitors represent a novel class of therapeutic agents with antitumor activity currently in clinical development. In this study, we tested the biological effects of the HDAC inhibitor MS-275 in various pre-clinical prostate cancer models both in'vitro and in vivo.
Methods:
In vitro cell proliferation XTT assay and protein expression analysis by Western blot were performed. In vivo tumor growth assessment in subcutaneous, orthotopic, and transgenic mouse models were conducted.
Results:
MS-275 significantly upregulated histone H3 acetylation and p21 gene expression in human prostate cancer cell lines. MS-275 exerted growth arrest in PC-3 and LNCaP cells, and induced cell death in DU-145 cells. Prostate specific antigen protein levels were increased by MS-275 in LAPC4 cell line. In vivo, MS-275 inhibited the growth of DU-145, LNCaP, and PC-3 in subcutaneous xenografts. MS-275 had also a significant inhibition of PC-3 cells growth in a mouse intratibial model. Molecular analysis showed increased histone acetylation and p21 expression in tumor samples from MS-275-treated mice. In transgenic adenocarcinoma of mouse prostate (TRAMP) mice, long-term treatment of MS-275 slowed the progression of prostate carcinomas with significant reduction in cell proliferation.
Conclusions:
Taken together, these data support the clinical testing of MS-275 for the treatment of prostate cancer.
Insights
Histone deacetylase (HDAC) inhibitor MS-275 demonstrated significant antitumor effects in preclinical prostate cancer models. This agent induced cell death, inhibited tumor growth, and slowed disease progression, supporting its clinical investigation.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Histone deacetylase (HDAC) inhibitors are a promising class of therapeutic agents with demonstrated antitumor activity.
- MS-275 is an HDAC inhibitor investigated for its potential in cancer treatment.
Purpose of the Study:
- To evaluate the biological effects of the HDAC inhibitor MS-275 in preclinical models of prostate cancer.
- To assess the in vitro and in vivo efficacy of MS-275.
Main Methods:
- In vitro studies included cell proliferation assays (XTT) and Western blot analysis for protein expression.
- In vivo studies involved tumor growth assessments in subcutaneous, orthotopic, and transgenic mouse models.
Main Results:
- MS-275 upregulated histone H3 acetylation and p21 expression in prostate cancer cell lines, causing growth arrest or cell death.
- In vivo, MS-275 inhibited tumor growth in xenograft models and slowed prostate carcinoma progression in TRAMP mice.
- Tumor samples from MS-275-treated mice showed increased histone acetylation and p21 expression.
Conclusions:
- MS-275 exhibits significant preclinical antitumor activity in prostate cancer models.
- The data support the further clinical evaluation of MS-275 for prostate cancer treatment.
