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.

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...

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Main Authors: Jay H Kalin, Abdulkerim Eroglu, Hua Liu, W David Holtzclaw, Irene Leigh, Charlotte M Proby, Jed W Fahey, Philip A Cole, Albena T Dinkova-Kostova
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0213095
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spelling doaj-f99b3105935445b2977644ef674fd19e2021-03-04T12:38:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021309510.1371/journal.pone.0213095Investigation 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 KalinAbdulkerim ErogluHua LiuW David HoltzclawIrene LeighCharlotte M ProbyJed W FaheyPhilip A ColeAlbena T Dinkova-KostovaCutaneous 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.https://doi.org/10.1371/journal.pone.0213095
collection DOAJ
language English
format Article
sources DOAJ
author Jay H Kalin
Abdulkerim Eroglu
Hua Liu
W David Holtzclaw
Irene Leigh
Charlotte M Proby
Jed W Fahey
Philip A Cole
Albena T Dinkova-Kostova
spellingShingle Jay H Kalin
Abdulkerim Eroglu
Hua Liu
W David Holtzclaw
Irene Leigh
Charlotte M Proby
Jed W Fahey
Philip A Cole
Albena T Dinkova-Kostova
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.
PLoS ONE
author_facet Jay H Kalin
Abdulkerim Eroglu
Hua Liu
W David Holtzclaw
Irene Leigh
Charlotte M Proby
Jed W Fahey
Philip A Cole
Albena T Dinkova-Kostova
author_sort Jay H Kalin
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.
title_short 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.
title_full 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.
title_fullStr 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.
title_full_unstemmed 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.
title_sort 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.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2019-01-01
description 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.
url https://doi.org/10.1371/journal.pone.0213095
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