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

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Hae-Ahm Lee ◽  
So-Min Park ◽  
Ki-Back Chu ◽  
Fu-Shi Quan ◽  
Thomas Kurz ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Apoptotic Cell ◽  
Therapeutic Option ◽  
Acanthamoeba Castellanii ◽  
Cyst Formation ◽  
Acanthamoeba Keratitis ◽  
Content Type ◽  
Cytopathic Effects ◽  
Transmission Electron

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.

scholarly journals In VitroEfficacy of Corifungin against Acanthamoeba castellanii Trophozoites and Cysts

2013 ◽  
Vol 58 (3) ◽  
pp. 1523-1528 ◽  
Author(s):  
Anjan Debnath ◽  
Josefino B. Tunac ◽  
Angélica Silva-Olivares ◽  
Silvia Galindo-Gómez ◽  
Mineko Shibayama ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Acanthamoeba Castellanii ◽  
Water Soluble ◽  
Content Type ◽  
Dense Granules ◽  
Transmission Electron ◽  
Novel Drugs ◽  
Amebic Encephalitis ◽  
Multiple Drugs

ABSTRACTPainful blinding keratitis and fatal granulomatous amebic encephalitis are caused by the free-living amebaeAcanthamoebaspp. Several prescription eye medications are used to treatAcanthamoebakeratitis, but the infection can be difficult to control because of recurrence of infection. For the treatment of encephalitis, no single drug was found useful, and in spite of the use of a combination of multiple drugs, the mortality rate remains high. Therefore, efficient, novel drugs are urgently needed for the treatment of amebic keratitis and granulomatous amebic encephalitis. In this study, we identified corifungin, a water-soluble polyene macrolide, as amebicidal.In vitro, it was effective against both the trophozoites and the cysts. Transmission electron microscopy ofAcanthamoeba castellaniiincubated with corifungin showed the presence of swollen mitochondria, electron-dense granules, degeneration of cytoplasm architecture, and loss of nuclear chromatin structure. These changes were followed by lysis of amebae. Corifungin also induced the encystment process ofA. castellanii. There were alterations in the cyst cell wall followed by lysis of the cysts. Corifungin is a promising therapeutic option for keratitis and granulomatous amebic encephalitis.

scholarly journals Behavior of Yersinia enterocolitica in the Presence of the Bacterivorous Acanthamoeba castellanii

2013 ◽  
Vol 79 (20) ◽  
pp. 6407-6413 ◽  
Author(s):  
E. Lambrecht ◽  
J. Baré ◽  
I. Van Damme ◽  
W. Bert ◽  
K. Sabbe ◽  
...  
Keyword(s):  
Yersinia Enterocolitica ◽  
Pathogenic Bacteria ◽  
Acanthamoeba Castellanii ◽  
Ecological Niches ◽  
Free Living ◽  
Content Type ◽  
Food Borne ◽  
Transmission Electron ◽  
Set Up ◽  
The Impact

ABSTRACTFree-living protozoa play an important role in the ecology and epidemiology of human-pathogenic bacteria. In the present study, the interaction betweenYersinia enterocolitica, an important food-borne pathogen, and the free-living amoebaAcanthamoeba castellaniiwas studied. Several cocultivation assays were set up to assess the resistance ofY. enterocoliticatoA. castellaniipredation and the impact of environmental factors and bacterial strain-specific characteristics. Results showed that allY. enterocoliticastrains persist in association withA. castellaniifor at least 14 days, and associations withA. castellaniienhanced survival ofYersiniaunder nutrient-rich conditions at 25°C and under nutrient-poor conditions at 37°C. Amoebae cultivated in the supernatant of oneYersiniastrain showed temperature- and time-dependent permeabilization. Intraprotozoan survival ofY. enterocoliticadepended on nutrient availability and temperature, with up to 2.8 log CFU/ml bacteria displaying intracellular survival at 7°C for at least 4 days in nutrient-rich medium. Transmission electron microscopy was performed to locate theYersiniacells inside the amoebae. AsYersiniaandAcanthamoebashare similar ecological niches, this interaction identifies a role of free-living protozoa in the ecology and epidemiology ofY. enterocolitica.

scholarly journals Autophagy Inhibitors as a Potential Antiamoebic Treatment for Acanthamoeba Keratitis

2015 ◽  
Vol 59 (7) ◽  
pp. 4020-4025 ◽  
Author(s):  
Eun-Kyung Moon ◽  
So-Hee Kim ◽  
Yeonchul Hong ◽  
Dong-Il Chung ◽  
Youn-Kyoung Goo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Acanthamoeba Keratitis ◽  
New Combination ◽  
Corneal Epithelial Cells ◽  
Content Type ◽  
Corneal Epithelial ◽  
Cytopathic Effects ◽  
Combination Treatments ◽  
Human Corneal Epithelial Cells ◽  
Significant Block

ABSTRACTAcanthamoebacysts are resistant to extreme physical and chemical conditions. Autophagy is an essential pathway for encystation ofAcanthamoebacells. To evaluate the possibility of an autophagicAcanthamoebaencystation mechanism, we evaluated autophagy inhibitors, such as 3-methyladenine (3MA), LY294002, wortmannin, bafilomycin A, and chloroquine. Among these autophagy inhibitors, the use of 3MA and chloroquine showed a significant reduction in the encystation ratio inAcanthamoebacells. Wortmannin also inhibited the formation of mature cysts, while LY294002 and bafilomycin A did not affect the encystation ofAcanthamoebacells. Transmission electron microscopy revealed that 3MA and wortmannin inhibited autophagy formation and that chloroquine interfered with the formation of autolysosomes. Inhibition of autophagy or autolysosome formation resulted in a significant block in the encystation inAcanthamoebacells. Clinical treatment with 0.02% polyhexamethylene biguanide (PHMB) showed high cytopathic effects onAcanthamoebatrophozoites and cysts; however, it also revealed high cytopathic effects on human corneal epithelial cells. In this study, we investigated effects of the combination of a low (0.00125%) concentration of PHMB with each of the autophagy inhibitors 3MA, wortmannin, and chloroquine onAcanthamoebaand human corneal epithelial cells. These new combination treatments showed low cytopathic effects on human corneal cells and high cytopathic effects onAcanthamoebacells. Taken together, these results provide fundamental information for optimizing the treatment ofAcanthamoebakeratitis.

scholarly journals Current and Emerging Therapeutics for Cutaneous T-Cell Lymphoma: Histone Deacetylase Inhibitors

Lymphoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Annabelle L. Rodd ◽  
Katherine Ververis ◽  
Tom C. Karagiannis
Keyword(s):  
T Cell ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Cell Lymphoma ◽  
Therapeutic Option ◽  
Hdac Inhibitors ◽  
Lymph Node Involvement ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
T Cell Lymphomas

Cutaneous T-cell lymphoma is a term that encompasses a spectrum of non-Hodgkin’s T-cell lymphomas with primary manifestations in the skin. It describes a heterogeneous group of neoplasms that are characterised by an accumulation of malignant T cells of the CD4 phenotype that have the propensity to home and accumulate in the skin, lymph nodes, and peripheral blood. The two most common variants of cutaneous T-cell lymphoma include mycosis fungoides and the leukemic variant, the Sézary syndrome. While numerous treatments are available for cutaneous T-cell lymphoma and have shown to have success in those with patch and plaque lesions, for those patients with tumour stage or lymph node involvement there is a significant decline in response. The relatively new therapeutic option with the use of histone deacetylase inhibitors is being advanced in the hope of decreasing morbidity and mortality associated with the disease. Histone deacetylase inhibitors have been shown to induce changes in gene expression, affecting cell cycle regulation, differentiation, and apoptosis. The aim of this paper is to discuss CTCL in the context of advances in CTCL treatment, specifically with HDAC inhibitors.

scholarly journals CKD-5, a novel pan-histone deacetylase inhibitor, synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Young Chang ◽  
Yun Bin Lee ◽  
Eun Ju Cho ◽  
Jeong-Hoon Lee ◽  
Su Jong Yu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Microarray Analysis ◽  
Histone Deacetylase Inhibitors ◽  
Therapeutic Option ◽  
Hypoxic Conditions ◽  
In Vivo Experiments ◽  
Induced Apoptosis ◽  
Hcc Cells

Abstract Background Histone deacetylase inhibitors (HDACIs) have distinctive epigenetic targets involved in hepatocarcinogenesis and chemoresistance. A recent phase I/II study reported the possibility of HDACI as a chemosensitizer in sorafenib-resistant patients. In this study, we evaluated whether CKD-5, a novel pan-HDACI, can potentiate the efficacy of sorafenib. Methods The anticancer effect of CKD-5 with and without sorafenib was evaluated in vitro using an MTS assay with human HCC cells (SNU-3058 and SNU-761) under both normoxic and hypoxic conditions. Microarray analysis was performed to investigate the mechanism of cell death, which was also evaluated by small interfering RNA (siRNA) transfection and subsequent immunoblot assays. In vivo experiments were conducted using two different murine HCC models. C3H mice implanted with MH134 cells and C57BL/6 mice implanted with RIL-175 cells were treated with weekly CKD-5 with and without sorafenib for 2 weeks. Results CKD-5 treatment significantly suppressed human HCC cell growth in both normoxic and hypoxic conditions. Microarray analysis and real-time PCR showed that CKD-5 treatment significantly increased peripherin expression in HCC cells and that downregulation of peripherin by siRNA decreased CKD-5-induced apoptosis. The combination of CKD-5 and sorafenib decreased cell viability more effectively than sorafenib or CKD-5 monotherapy in human and murine HCC cells. The effectiveness of the combination therapy was consistently demonstrated in the animal models. Histological and biochemical analyses demonstrated good tolerance of CKD-5 plus sorafenib in vivo. Conclusion CKD-5 may enhance sorafenib efficacy through epigenetic regulation. The combination of CKD-5 and sorafenib might be a novel therapeutic option for the treatment of HCC.

scholarly journals Kinetic Analysis of Acanthamoeba castellanii Infected with Giant Viruses Quantitatively Revealed Process of Morphological and Behavioral Changes in Host Cells

2021 ◽  
Author(s):  
Sho Fukaya ◽  
Masaharu Takemura
Keyword(s):  
Phase Contrast ◽  
Acanthamoeba Castellanii ◽  
Time Lapse ◽  
Infection Process ◽  
Behavioral Changes ◽  
Host Cells ◽  
Content Type ◽  
Host Interactions ◽  
Cytopathic Effects ◽  
Giant Viruses

Quantitative analysis of the infection process is important for a better understanding of viral infection strategies and virus-host interactions. Here, an image analysis of the phase-contrast time-lapse movies displayed quantitative differences in the process of cytopathic effects due to the four giant viruses in Acanthamoeba castellanii , which were previously unclear.

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