Academic Journal
Histone deacetylase inhibitors enhance the amoebicidal activity of amphotericin B against Naegleria fowleri.
| Τίτλος: | Histone deacetylase inhibitors enhance the amoebicidal activity of amphotericin B against Naegleria fowleri. |
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| Συγγραφείς: | Lee HA; Department of Medical Zoology, Kyung Hee University College of Medicine, Seoul, Republic of Korea., Jo HJ; Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea., Hong JY; Department of Periodontology, Kyung Hee University College of Dentistry, Periodontal-Implant Clinical Research Institute, Kyung Hee University Dental Hospital, Seoul, Republic of Korea., Quan FS; Department of Medical Zoology, Kyung Hee University College of Medicine, Seoul, Republic of Korea., Moon EK; Department of Medical Zoology, Kyung Hee University College of Medicine, Seoul, Republic of Korea. Electronic address: ekmoon@khu.ac.kr. |
| Πηγή: | International journal for parasitology. Drugs and drug resistance [Int J Parasitol Drugs Drug Resist] 2026 Aug; Vol. 31, pp. 100664. Date of Electronic Publication: 2026 Aug 03. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101576715 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-3207 (Electronic) Linking ISSN: 22113207 NLM ISO Abbreviation: Int J Parasitol Drugs Drug Resist Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Amsterdam] : Elsevier, 2011- |
| Ιατρικοί όροι (MeSH): | Histone Deacetylase Inhibitors*/pharmacology , Naegleria fowleri*/drug effects , Amphotericin B*/pharmacology , Antiprotozoal Agents*/pharmacology , Amebicides*/pharmacology, Apoptosis/drug effects ; Trophozoites/drug effects ; Drug Synergism ; Humans ; Animals |
| Περίληψη: | Naegleria fowleri is a free-living amoeba that causes a rare but almost always fatal brain infection known as primary amoebic meningoencephalitis (PAM). Although amphotericin B (AmB) is considered the primary treatment for PAM, it is often recommended in combination with several other drugs due to side effects associated with high concentrations. In this study, we investigated whether histone deacetylase inhibitors (HDACis) enhance the amoebicidal activity of AmB against N. fowleri. Anti-proliferative and cytotoxic activities were assessed using the cell counting kit and lactate dehydrogenase assays, respectively, and apoptosis induction was evaluated by flow cytometry. Class-specific HDACis, including class I inhibitors MS275 and MGCD0103 and a class II inhibitor MC1568, showed minimal effects on trophozoite viability. In contrast, the pan-HDACis SAHA and JNJ significantly reduced trophozoite viability in a dose- and time-dependent manner. Furthermore, 10 μM SAHA and JNJ significantly reduced the encystation ratio of N. fowleri. Combined treatment with low doses of HDACi (1 μM) and AmB (0.5 μM) produced stronger amoebicidal and pro-apoptotic effects than either agent alone. These combination treatments also exhibited low cytopathic effects on human brain tumor cells. These findings suggest that SAHA and JNJ, particularly in combination with AmB, hold promise as therapeutic candidates against N. fowleri infection while potentially mitigating the severe side effects associated with AmB. (Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper. |
| Contributed Indexing: | Keywords: Amphotericin B; HDAC inhibitor; N. fowleri; PAM |
| Substance Nomenclature: | 0 (Histone Deacetylase Inhibitors) 7XU7A7DROE (Amphotericin B) 0 (Antiprotozoal Agents) 0 (Amebicides) |
| Entry Date(s): | Date Created: 20260805 Date Completed: 20260817 Latest Revision: 20260817 |
| Update Code: | 20260818 |
| PubMed Central ID: | PMC13470574 |
| DOI: | 10.1016/j.ijpddr.2026.100664 |
| PMID: | 42556068 |
| Βάση Δεδομένων: | MEDLINE |
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