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Cited by 36T-cell and Retrovirus StudiesHistone Deacetylase Inhibitors ResearchViral-associated cancers and disorders

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Efficacy of novel histone deacetylase inhibitor, AR42, in a mouse model of, human T-lymphotropic virus type 1 adult T cell lymphoma

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Zimmerman, Bevin, Sargeant, Aaron, Landes, Kristina, Fernandez, Soledad A., Chen, Ching-Shih, Lairmore, Michael D.·2011·Leukemia Research
DOI 10.1016/j.leukres.2011.07.015PMC PMC3191315
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Abstract

Human T-lymphotropic virus type 1 (HTLV-1) causes a variety of forms of adult T-cell leukemia/lymphoma (ATL), a refractory CD4+/CD25+ T-cell malignancy. Novel approaches to treat ATL patients are required due to the resistance of ATL to conventional chemotherapies. Histone deacetylase inhibitors (HDACi), which induce histone hyperacetylation leading to chromatin remodeling and reactivation of transcriptionally repressed genes have shown efficacy against a variety of cancers. Herein, we tested if valproic acid and the novel orally bioavailable HDACi, AR-42 reduced the proliferation of ATL cell lines by promoting apoptosis and histone hyperacetylation. Both compounds were cytotoxic and elicited a dose dependent increase in cytochrome C and cleaved Poly (ADP-ribose) polymerase (PARP) indicating the induction of cell death by apoptosis and promoted acetylation of histone H3 in both MT-2 and C8166 cell lines. We then evaluated the effects of AR-42, for survival in an ATL NOD/SCID mouse model. A dietary formulation of AR-42 prolonged survival of ATL engrafted mice compared to controls. Our data provide new directions for the treatment of ATL and support the further development of AR-42 against HTLV-1-associated lymphoid malignancies.

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  • HDACIs have anti-leukaemic potential in HTLV-1-transformed and ATL-derived cell lines by blocking the Notch pathway to decrease NF-κB and induce apoptosis.

    “The anti-leukaemic potential of HDACIs (including valproic acid, vorinostat, romidepsin, panobinostat, and entinostat) has been characterised by multiple in vitro studies in HTLV-1-transformed and ATL-derived cell lines by blocking the Notch pathway to decrease NF-κB and induces apoptosis [226,227].”

    From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [227]

    Results §3.2 reports that valproic acid and AR-42 induced apoptosis in the HTLV-1-related MT-2 and C8166 cell lines, supporting the anti-leukaemic potential of HDAC inhibitors. The paper does not report that these effects occur by blocking Notch or decreasing NF-κB, and it does not establish the claim for all the named inhibitors. (LLM, conf=0.88)

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Research works printed but not linked: 31

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Metadata

Authors
Zimmerman, B., Sargeant, A., Landes, K., Fernandez, S. A., Chen, C.-S., & Lairmore, M. D.
Affiliations
  • The Ohio State University (US)
  • The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
ORCID
Venue
Leukemia Research
Publisher
Elsevier BV
Published
2011-11
Volume
35
Issue
11
Pages
1491-1497
ISSN
0145-2126 (ISSN-L)
DOI
10.1016/j.leukres.2011.07.015
PMC
PMC3191315
OpenAlex
W2080921259
Cited by
36
References
2
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 4
FWCI
1.56
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Leukemia Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (CA-70529, P01CA100730)
  • National Center for Research Resources (K01RR023965)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
Keywords
adult T-cell leukemia/lymphoma, HTLV-1, histone deacetylase inhibitors, AR-42, valproic acid, histone hyperacetylation, apoptosis, cytochrome c release, PARP cleavage, histone H3 acetylation, MT-2 cell line, NOD/SCID mouse model, oral bioavailability, antitumor efficacy
MeSH terms
Acetylation, Adult, Animals, Enzyme Inhibitors, Female, Histone Deacetylases, Histones, Humans, Phenylbutyrates, Poly(ADP-ribose) Polymerases, T-Lymphocytes, Tumor Cells, Cultured, Valproic Acid, Blotting, Western, Human T-lymphotropic virus 1, Leukemia-Lymphoma, Adult T-Cell, Survival Rate, Mice, SCID, Mice, Inbred NOD, Cytochromes c, Mice

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