Investigation into the use of histone deacetylase inhibitor MS-275 as a topical agent for the prevention and treatment of cutaneous squamous cell carcinoma in an SKH-1 hairless mouse model

Jay H. Kalin (Lead / Corresponding author), Abdulkerim Eroglu, Hua Liu, W. David Holtzclaw, Irene Leigh, Charlotte M. Proby, Jed W. Fahey, Philip A. Cole, Albena T. Dinkova-Kostova (Lead / Corresponding author)

Research output: Contribution to journalArticle

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Abstract

Cutaneous squamous cell carcinomas are a common form of highly mutated keratinocyte skin cancers that are of particular concern in immunocompromised patients. Here we report on the efficacy of topically applied MS-275, a clinically used histone deacetylase inhibitor, for the treatment and management of this disease. At 2 mg/kg, MS-275 significantly decreased tumor burden in an SKH-1 hairless mouse model of UVB radiation-induced skin carcinogenesis. MS-275 was cell permeable as a topical formulation and induced histone acetylation changes in mouse tumor tissue. MS-275 was also effective at inhibiting the proliferation of patient derived cutaneous squamous cell carcinoma lines and was particularly potent toward cells isolated from a regional metastasis on an immunocompromised individual. Our findings support the use of alternative routes of administration for histone deacetylase inhibitors in the treatment of high-risk squamous cell carcinoma which may ultimately lead to more precise delivery and reduced systemic toxicity.

Original languageEnglish
Article numbere0213095
Pages (from-to)1-13
Number of pages13
JournalPLoS ONE
Volume14
Issue number3
DOIs
Publication statusPublished - 13 Mar 2019

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Hairless Mouse
histone deacetylase
Histone Deacetylase Inhibitors
squamous cell carcinoma
Squamous Cell Carcinoma
animal models
Skin
immunocompromised population
Tumors
neoplasms
keratinocytes
acetylation
skin (animal)
histones
Acetylation
metastasis
carcinogenesis
disease control
Immunocompromised Host
Skin Neoplasms

Cite this

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title = "Investigation into the use of histone deacetylase inhibitor MS-275 as a topical agent for the prevention and treatment of cutaneous squamous cell carcinoma in an SKH-1 hairless mouse model",
abstract = "Cutaneous squamous cell carcinomas are a common form of highly mutated keratinocyte skin cancers that are of particular concern in immunocompromised patients. Here we report on the efficacy of topically applied MS-275, a clinically used histone deacetylase inhibitor, for the treatment and management of this disease. At 2 mg/kg, MS-275 significantly decreased tumor burden in an SKH-1 hairless mouse model of UVB radiation-induced skin carcinogenesis. MS-275 was cell permeable as a topical formulation and induced histone acetylation changes in mouse tumor tissue. MS-275 was also effective at inhibiting the proliferation of patient derived cutaneous squamous cell carcinoma lines and was particularly potent toward cells isolated from a regional metastasis on an immunocompromised individual. Our findings support the use of alternative routes of administration for histone deacetylase inhibitors in the treatment of high-risk squamous cell carcinoma which may ultimately lead to more precise delivery and reduced systemic toxicity.",
author = "Kalin, {Jay H.} and Abdulkerim Eroglu and Hua Liu and Holtzclaw, {W. David} and Irene Leigh and Proby, {Charlotte M.} and Fahey, {Jed W.} and Cole, {Philip A.} and Dinkova-Kostova, {Albena T.}",
note = "Funding: We thank the NIH (GM62437), Cancer Research UK (C20953/A18644), the Biotechnology and Biological Sciences Research Council (BB/L01923X/1), and the British Skin Foundation (7015) for financial support.",
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Investigation into the use of histone deacetylase inhibitor MS-275 as a topical agent for the prevention and treatment of cutaneous squamous cell carcinoma in an SKH-1 hairless mouse model. / Kalin, Jay H. (Lead / Corresponding author); Eroglu, Abdulkerim; Liu, Hua; Holtzclaw, W. David; Leigh, Irene; Proby, Charlotte M.; Fahey, Jed W.; Cole, Philip A.; Dinkova-Kostova, Albena T. (Lead / Corresponding author).

In: PLoS ONE, Vol. 14, No. 3, e0213095, 13.03.2019, p. 1-13.

Research output: Contribution to journalArticle

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AU - Kalin, Jay H.

AU - Eroglu, Abdulkerim

AU - Liu, Hua

AU - Holtzclaw, W. David

AU - Leigh, Irene

AU - Proby, Charlotte M.

AU - Fahey, Jed W.

AU - Cole, Philip A.

AU - Dinkova-Kostova, Albena T.

N1 - Funding: We thank the NIH (GM62437), Cancer Research UK (C20953/A18644), the Biotechnology and Biological Sciences Research Council (BB/L01923X/1), and the British Skin Foundation (7015) for financial support.

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