Publications by authors named "Hui-Jung Jung"

6 Publications

  • Page 1 of 1

Juglone induces cell death of Acanthamoeba through increased production of reactive oxygen species.

Exp Parasitol 2015 Dec 7;159:100-6. Epub 2015 Sep 7.

Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea. Electronic address:

Juglone (5-hydroxy-1,4-naphthoquinone) is a major chemical constituent of Juglans mandshruica Maxim. Recent studies have demonstrated that juglone exhibits anti-cancer, anti-bacterial, anti-viral, and anti-parasitic properties. However, its effect against Acanthamoeba has not been defined yet. The aim of this study was to investigate the effect of juglone on Acanthamoeba. We demonstrate that juglone significantly inhibits the growth of Acanthamoeba castellanii at 3-5 μM concentrations. Juglone increased the production of reactive oxygen species (ROS) and caused cell death of A. castellanii. Inhibition of ROS by antioxidant N-acetyl-l-cysteine (NAC) restored the cell viability. Furthermore, our results show that juglone increased the uptake of mitochondrial specific dye. Collectively, these results indicate that ROS played a significant role in the juglone-induced cell death of Acanthamoeba.
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http://dx.doi.org/10.1016/j.exppara.2015.09.005DOI Listing
December 2015

Chloroquine has a cytotoxic effect on Acanthamoeba encystation through modulation of autophagy.

Antimicrob Agents Chemother 2014 Oct 11;58(10):6235-41. Epub 2014 Aug 11.

Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea

Encystation of Acanthamoeba castellanii is associated with resistance to chemotherapeutic agents. Blocking the encystation process could potentiate the efficacy of chemotherapeutic agents and biocides. During encystation, autophagy is highly stimulated and required for proper encystation of Acanthamoeba. In this study, the cytotoxic effect of chloroquine, a well-known autophagy-inhibitory drug, was tested in A. castellanii. Chloroquine was able to selectively reduce cell survival during the encystation of A. castellanii. However, A. castellanii trophozoites and mature cysts were resistant to chloroquine. Chloroquine treatment led to an increase in the number and size of lysosomes in encysting cells. Moreover, chloroquine inhibited the degradation of long-lived proteins in the encysting cells. Decreased autophagic flux, indicated by an increased number of lysosomes and decreased degradation of long-lived proteins, may be the mechanism by which cell death is induced by chloroquine in encysting Acanthamoeba. These results suggest a potential novel therapeutic application of chloroquine as an anti-Acanthamoeba drug. Our findings also suggest that targeting autophagy could be a therapeutic strategy against Acanthamoeba infection.
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http://dx.doi.org/10.1128/AAC.03164-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187977PMC
October 2014

Translational suppression of HIF-1α by miconazole through the mTOR signaling pathway.

Cell Oncol (Dordr) 2014 Aug 29;37(4):269-79. Epub 2014 Jul 29.

Department of Microbiology, Keimyung University School of Medicine, 1095 Dalgubeol-daero, Dalseo-gu, Daegu, 704-701, Republic of Korea.

Background: Miconazole is an imidazole antifungal agent that has amply been used in the treatment of superficial mycosis. Preliminary data indicate that miconazole may also induce anticancer effects. As yet, however, little is known about the therapeutic efficacy of miconazole on cancer and the putative mechanism(s) involved. Here, we show that miconazole suppresses hypoxia inducible factor-1α (HIF-1α) protein translation in different cancer-derived cells.

Methods: The effect of miconazole on HIF-1α expression was examined by Western blotting and reverse transcriptase polymerase chain reaction assays in human U87MG and MCF-7 glioma and breast cancer-derived cell lines, respectively. The transcriptional activity of the HIF-1 complex was confirmed using a luciferase assay. To assess whether angiogenic factors are increased under hypoxic conditions in these cells, vascular endothelial growth factor (VEGF) levels were measured by ELISA. Metabolic labeling was performed to examine HIF-1α protein translation and global protein synthesis. The role of the mammalian target of rapamycin (mTOR) signaling pathway was examined to determine translation regulation of HIF-1α after miconazole treatment.

Results: Miconazole was found to suppress HIF-1α protein expression through post-transcriptional regulation in U87MG and MCF-7 cells. The suppressive effect of HIF-1α protein synthesis was found to be due to inhibition of mTOR. Miconazole significantly inhibited the transcriptional activity of the HIF-1 complex and the expression of its target VEGF. Moreover, miconazole was found to suppress global protein synthesis by inducing phosphorylation of the translation initiation factor 2α (eIF2α).

Conclusion: Our data indicate that miconazole plays a role in translational suppression of HIF-1α. We suggest that miconazole may represent a novel therapeutic option for the treatment of cancer.
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http://dx.doi.org/10.1007/s13402-014-0182-8DOI Listing
August 2014

Minocycline inhibits angiogenesis in vitro through the translational suppression of HIF-1α.

Arch Biochem Biophys 2014 Mar 8;545:74-82. Epub 2014 Jan 8.

Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea. Electronic address:

Minocycline was recently found to be effective against cancer. However, the precise molecular mechanisms of minocycline in cancer are poorly understood. Hypoxia-inducible factor-1 (HIF-1, a heterodimeric transcription factor composed of HIF-1α and β) activates the transcription of genes that are involved in angiogenesis in cancer. In this study, we found that minocycline significantly inhibits HIF-1α protein expression and suppresses HIF-1 transcriptional activity. The tube formation assay showed that minocycline has anti-angiogenic activity and suppresses hypoxia-induced vascular endothelial growth factor (VEGF) expression. The metabolic labeling assay showed that minocycline reduces HIF-1α protein translation and global protein synthesis. In addition, minocycline suppresses mTOR signaling and increases the phosphorylation of eIF2α, which is known to be related to the translational regulation of HIF-1α expression. These findings collectively indicate that minocycline is a potential inhibitor of HIF-1α and provide new insight into the discovery of drugs for cancer treatment.
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http://dx.doi.org/10.1016/j.abb.2013.12.023DOI Listing
March 2014

Pentamidine reduces expression of hypoxia-inducible factor-1α in DU145 and MDA-MB-231 cancer cells.

Cancer Lett 2011 Apr 12;303(1):39-46. Epub 2011 Feb 12.

Chronic Disease Research Center, School of Medicine, Keimyung University, Daegu 704-701, Republic of Korea.

Pentamidine is an aromatic diamine used for the treatment of human protozoa infections. Recently, pentamidine has been reported to exhibit anticancer properties. In this study, we report that pentamidine inhibits expression of hypoxia-inducible factor (HIF)-1α in cancer cells. Pentamidine decreased HIF-1α protein translation and enhanced its protein degradation in DU145 prostate cancer and MDA-MB-231 breast cancer cells. In parallel with reduction of de novo synthesis of HIF-1α, pentamidine was able to suppress global protein translation, an effect accompanied by the reduction of eIF4F complex formation and also the induction of eIF2α phosphorylation. These results show that pentamidine is a potential inhibitor of HIF-1α and its potential as a cancer therapeutic reagent warrants further study.
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http://dx.doi.org/10.1016/j.canlet.2011.01.008DOI Listing
April 2011

Silibinin inhibits expression of HIF-1alpha through suppression of protein translation in prostate cancer cells.

Biochem Biophys Res Commun 2009 Dec 22;390(1):71-6. Epub 2009 Sep 22.

Chronic Disease Research Center, School of Medicine, Keimyung University, Daegu 700-712, Republic of Korea.

Silibinin is a polyphenolic flavonoid isolated from the milk thistle (Silybum marianum) and is reported to exhibit anticancer properties. Recently, it has been reported that silibinin inhibits hypoxia-inducible factor-1alpha (HIF-1alpha) expression in cancer cells. However, the precise mechanism by which silibinin decreases HIF-1 expression is not fully understood. In this study, silibinin inhibited basal and hypoxia induced expression levels of HIF-1alpha protein in LNCaP and PC-3 prostate cancer cells, while the rate of HIF-1alpha protein degradation and mRNA levels were not affected. We found that the decrease in HIF-1 protein by silibinin correlated with suppression of de novo synthesis of HIF-1alpha protein. Silibinin inhibited global protein synthesis coincided with reduction of eIF4F complex formation and induction of phosphorylation of the translation initiation factor 2alpha (eIF-2alpha) which can cause inhibition of general protein synthesis. These results suggest that silibinin's activity to inhibit HIF-1alpha protein expression is associated with the suppression of global protein translation.
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http://dx.doi.org/10.1016/j.bbrc.2009.09.068DOI Listing
December 2009