Application of Histone Deacetylase Inhibitors MPK472 and KSK64 as a Potential Treatment Option for Acanthamoeba Keratitis

组蛋白去乙酰化酶抑制剂 MPK472 和 KSK64 作为棘阿米巴角膜炎潜在治疗选择的应用

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作者:Hae-Ahm Lee, So-Min Park, Ki-Back Chu, Fu-Shi Quan, Thomas Kurz, Marc Pflieger, Eun-Kyung Moon

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 (HDACis) are involved in cell proliferation, differentiation, and apoptotic cell death. In this study, the effects of HDACis such as MPK472 and KSK64 on Acanthamoeba castellanii trophozoites and cysts were observed. MPK472 and KSK64 showed at least 60% amoebicidal activity against Acanthamoeba trophozoites at a concentration of 10 μM upon 8 h of treatment. Neither of the two HDACis affected mature cysts, but significant amoebicidal activities (36.4 and 33.9%) were observed against encysting Acanthamoeba following treatment with 5 and 10 μM HDACis for 24 h. Light microscopy and transmission electron microscopy results confirmed that the encystation of Acanthamoeba was inhibited by the two HDACis. In addition to this, low cytopathic effects on human corneal epithelial (HCE) cells were observed following treatment with MPK472 and KSK64 for 24 h. Our results indicate that the HDACis MPK472 and KSK64 could be used as new candidates for the development of an optimal therapeutic option for AK.

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