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)

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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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