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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2019-01-01
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Online Access: | https://doi.org/10.1371/journal.pone.0213095 |
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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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