Application of Histone Deacetylase Inhibitors MPK472 and KSK64 as a Potential Treatment Option for Acanthamoeba Keratitis
- 17 November 2020
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 64 (12)
- https://doi.org/10.1128/aac.01506-20
Abstract
Treatment of Acanthamoeba keratitis (AK) is difficult because Acanthamoeba cysts are resistant to drugs and as such, successful treatment requires an effective approach that inhibits cyst formation. Histone deacetylase inhibitors (HDACi) are involved in cell proliferation, differentiation, and apoptotic cell death. In this study, the effects of HDACi such as MPK472 and KSK64 on A. castellanii trophozoites and cysts were observed. MPK472 and KSK64 showed at least 60% amoebicidal activity against Acanthamoeba trophozoite at a concentration of 10 μM upon 8 h. Neither of the two HDACi affected mature cysts, but significant amoebicidal activities (36.4% and 33.9%) were observed against encysting Acanthamoeba following treatment with 5 and 10 μM HDACi for 24 h. Light microscopy and transmission electron microscopy results confirmed that the encystation of Acanthamoeba was inhibited by the two HDACi. In addition to this, low cytopathic effects on human corneal epithelial (HCE) cells were observed following MPK472 and KSK64 treatment for 24 h. Our results indicate that the HDACi MPK472 and KSK64 could be used as new candidates for the development of an optimal therapeutic option for AK.Funding Information
- National Research Foundation of Korea (2018R1A6A1A03025124)
- National Research Foundation of Korea (2020R1A2C1005345)
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