• The Journal of the Korean Society for Microbiology
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• v.34 no.6
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• pp.501-512
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• 1999

Gliotoxin, a fungal metabolite, is one of the epipolythiodioxopiperazine classes and has a variety of effects including immunomodulatory and apoptotic agents. This study is designed to evaluate the effect of zinc on gliotoxin-induced death of HL-60 cells. Here, we demonstrated that treatment of gliotoxin decreased cell viability in a dose and time-dependent manner. Gliotoxin-induced cell death was confirmed as apoptosis characterized by chromatin margination, fragmentation and ladder-pattern digestion of genomic DNA. Gliotoxin increased the proteolytic activities of caspase 3, 6, 8, and 9. Caspase-3 activation was further confirmed by the degradation of procaspase-3 and PARP in gliotoxin-treated HL-60 cells. Zinc compounds including $ZnCl_2$ and $ZnSO_4$ markedly inhibited gliotoxin-induced apoptosis in HL-60 cells (from 30% to 90%). Consistent with anti-apoptotic effects, zinc also suppressed the enzymatic activities of caspase-3 and -9 proteases. In addition, cleavage of both PARP and procaspase 3 in gliotoxin-treated HL-60 cells was inhibited by the addition of zinc compounds. We further demonstrated that expression of Fas ligand by gliotoxin was suppressed by zinc compounds. These data suggest that zinc may prevent gliotoxin-induced apoptosis via inhibition of Fas ligand expression as well as suppression of caspase family cysteine proteases-3 and -9 in HL-60 cells.

• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.744-754
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• 2020

We investigated the whether endurance exercise and MitoQ intake mediated neuroprotection are associated with mitochondrial function in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine(MPTP) -induced mice model of Parkinson's disease. C57BL/6 male mice were randomly assigned to five groups: Normal Conrol(NC, n=10), MPTP Control(MC, n=10), MPTP +MitoQ(MQ, n=10), MPTP + Exercise(ME, n=10) and MPTP + MitoQ + Exercise(MQE, n=10). Exercise intervention groups performed the treadmill exercise for 5days/week for 5 weeks with gradual increase of intensity. MitoQ intake groups consumed the MitoQ at a concentration of 250μmol by dissolving with water during experiment period. Our data demonstrated that ME and MQE group restored MPTP-induced motor dysfunction. In addition, treatment groups(MQ, ME and MQE) increased tyrosine hydroxylase levels, and suppressed the accumulation of α-synuclein levels. Futhermore, treatment groups modulated the mitochondrial function such as upregulated mitochondrial biogenesis, increased antioxidant enzyme, enhanced a anti-apoptotic protein(e.g., BCL2), and reduced a pro-apoptotic protein(e.g., BAX). Taken together, these results suggested that endurance exercise and MitoQ intake-mediated increase in mitochondrial function contributes to improvement of aggravated dopaminergic neuronal, resulting in attenuation of motor function of Parkinson's disease.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.4
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• pp.672-678
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• 2002

Oxidative stress contributes to cellular injury following clinical and experimental ischemia/reperfusion scenarios. Oxidative injury can induce cellular and nuclear damages that result in apoptotic cell death. We tested the hypothesis that the catechin flavonoid of (-)epigallocatechin gallate, a green tea polyphenol, inhibits hydrogen peroxide ($H_2O$$_2$)-induced apoptosis in human umbilical vein endothelial cells. The effect of apigenin, a flavone found in citrus fruits, on apoptosis parameters was also examined. A 30 min pulse treatment with 0.25 mM $H_2O$$_2$ decreased endothelial cell viability within 24 hrs by > 30% ; this was associated with nuclear condensation and biochemical DNA damage consistent with programmed cell death. In the 0.25 mM $H_2O$$_2$apoptosis model, 50${\mu}{\textrm}{m}$ (-)epigallocatechin gallate markedly increased cell viability with a reduction in the nuclear condensation and DNA fragmentation. In contrast, equimicromolar apigenin increased cell loss with intense DNA laddering, positive nick-end labeling and Hoechst 33258 staining. Thus, polyphenolic (-)epigallocatechin gallate, but not apigenin flavone, qualify as an antioxidant in apoptosis models caused by oxidative stress. Further work is necessary for elucidating the anti-apoptotic mechanisms of polyphenolic catechins.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.7
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• pp.901-906
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• 2012

The purpose of this study was to elucidate the anti-proliferative effect and the mechanisms underlying apoptosis induced by a methanol extracts from Ishige sinicola (ISE) in HeLa cells. ISE treatment for 24 hr significantly inhibited cell viability in a dose-dependent manner. Apoptosis was detected by Hoechst 33258 staining and an annexin V/PI assay after 24 hr treatment. Moreover, ISE treatment triggered the cleavage of caspase-8, -9, -3, and poly(ADP-ribose) polymerase (PARP) in dose-dependent and time-dependent manners. In addition, z-VAD-fmk, a general caspase inhibitor, blocked ISE-induced cell death. Taken together, these results suggest that ISE-induced apoptosis is mediated by the activation of a caspase cascade in HeLa cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.394-402
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• 2003

This study was designed to investigate the protective effect of Bojungmyunyuk-dan(BJMY-Dan) on the cisplatin-induced cytotoxicity of primary rat astrocytes. BJMY-Dan is an oriental herbal prescription for its ability to recover protective effects against anti-cancer chemotherapies. After astrocytes were treated cisplatin, MTT assay was performed for cell viability test. To explore the mechanism of cytotoxicity, I used the several measures of apoptosis to determine whether this processes was involved in cisplatin-induced cell damage in astrocytes. Also, astrocytes were treated with BJMY-Dan and then, followed by the addition of cisplatin. Cisplatin decreased the viability of astrocytes in a dose and time-dependent manner. BJMY-Dan increased the viability of astrocytes treated cisplatin. Astrocytes treated cisplatin were revealed as apoptosis characterized by nuclear staining and flow cytometry. BJMY-Dan protected astrocytes from cisplatin-induced nuclear fragmentation and chromatin condensation. Also, caspase-3 and caspase-9 proteases were activated in astrocytes by cisplatin. BJMY-Dan inhibited the activation of caspase proteases in cisplatin-treated astrocytes. Cleavage of [poly(ADP-ribose) polymerase](PARP) was occurred at 12hr after treatment of cisplatin in astrocytes. BJMY-Dan recovered the cleavage of PARP in cisplatin-treated astrocytes. Also, BJMY-Dan inhibited the activation of pro-apoptotic factor, Bak by cisplatin. Lastly, astrocytes stained with JC-1 and Rhodamine 123 were photographed by fluorescence microscope to visualize changes of mitochondrial membrane permeability transition(MPT) during treatment with cisplatin for 24hr. BJMY-Dan recovered the change of MPT by cisplatin in astrocytes. According to above results, BJMY-Dan may protect astrocytes from cytotoxicity induced by chemotherapeutic agents, including cisplatin.

• Korean Journal of Food Science and Technology
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• v.37 no.2
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• pp.221-227
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• 2005

Apoptosis of Prunus salicina Lindl. cv. Soldam, which possesses hematopoiesis, osteoporosis prevention, and antimutagenic effects, at different growth stages was evaluated. Cytotoxic effect of acetone extracts of immature fruits against various tumor cell lines was higher than that of mature fruits, particularly in hormone-independent human breast cancer, MDA-MB-231 cell line. Immature fruit extract increased expression level of pro-apoptotic protein Bax and reduced that of anti-apoptotic protein Bcl-2, and stimulated caspase-3 activity in MDA-MB-231 cells. Results suggest immature fruit of P. salicina Lindl. cv. soldam to be natural source for development of functional food and medical agents to prevent human breast cancer.

• Korean Journal of Agricultural Science
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• v.49 no.2
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• pp.175-184
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• 2022

The present study investigated the neuroprotective effects of Coreopsis lanceolate extract against hydrogen-peroxide (H₂O₂)-induced oxidative damage and cell death in pheochromocytoma 12 (PC12) cells. Reactive oxygen species (ROS), 2,2'-azinobis (3-ethylbebzothiazoloine-6-sulfonic acid) diammonium salt, and 1,1-diphenyl-2-picrrylhydrazyl radical scavenging activities, as well as the expression levels of proteins associated with oxidative damage and cell death were investigated. According to the results, C. lanceolate extract exhibited inhibitory activity against intracellular ROS generation and cell-damaging effects induced by hydroxyl radicals in a dose-dependent manner. Total phenolic and flavonoid contents were 22.3 mg·g^-1 gallic acid equivalent and 16.2 mg·g^-1 catechin equivalent, respectively. Additionally, a high-performance liquid chromatography (HPLC) assay based on the internal standard method used to detect phenolic compounds. The phenolic compounds identified in C. lanceolata extract contained (+)-catechin hydrate (5.0 ± 0.0 mg·g^-1), ferulic acid (1.6 ± 0.0 mg·g^-1), chlorogenic acid (1.5 ± 0.0 mg·g^-1), caffeic acid (1.2 ± 0.0 mg·g-1), naringin (0.9 ± 0.0 mg·g^-1), and p-coumaric acid (0.5 ± 0.0 mg·g^-1). C. lanceolata extract attenuated pro-apoptotic Bax expression levels and enhanced the expression levels of anti-apoptotic Bcl-2, caspase-3, and caspase-9 proteins. Therefore, C. lanceolata is a potential source of materials with neuroprotective properties against neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases.

• Toxicological Research
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• v.25 no.4
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• pp.181-188
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• 2009

Uncontrolled cell growth and increased cell proliferation are major features of cancer that are dependent on the stable structure and dynamics of the cytoskeleton. Since stable cytoskeleton structure and dynamics are partly regulated by myosin light chain kinase (MLCK), many current studies focused on MLCK inhibition as a chemotherapeutic target. As a potent and selective MLCK inhibitor, ML-7 [1-(5-iodonaphthalene-1-sulfonyl)-1 H-hexahydro-1,4-diazapine hydrochloride] is a promising candidate for an anticancer agent, which would induce apoptosis as well as prevents invasion and metastasis in certain types of cancer cells. This study assessed cytotoxic effects of ML-7 against HL-60 cells and therapeutic efficacy of ML-7 as a potential antileukemia agent. Trypan-blue exclusion assays showed dose- and time- dependent decreases in ML-7 treated HL-60 cells (p<0.05). Comet assays revealed a significant increase in DNA damage in HL-60 cells after treatment with $40{\mu}M$ ML-7 for 2h. Sub-G1 fractions, analyzed by flow cytometry increased in a dose-dependent manner, suggesting that ML-7 can induce apoptotic cell death in HL-60 cells. ML-7 was selectively cytotoxic towards HL-60 cells; not affecting normal human lymphocytes. That selective effect makes it a promising potential anti-leukemia agent. In addition, anticancer efficacy of ML-7 in combination with flavonoids (genistein or quercetin) or anticancer drugs (cisplatin or Ara-C) against HL-60 cells was assessed. Combination of ML-7 with flavonoids increased the anti-cancer effect of ML-7 to a greater extent than combination with the anticancer drugs. This implies that ML-7 in combination with flavonoids could increase the efficacy of anticancer treatment, while avoiding side effects cansed by conventional anticancer drug-containing combination chemotherapy.

• Reproductive and Developmental Biology
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• v.38 no.3
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• pp.115-121
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• 2014

Humulus japonicus is an ornamental plant in the Cannabaceae family. Although the mode of action of Humulus japonicus is not fully understood, a strong relationship was observed between anti-inflammatory and anticancer in some types of cells. Recent studies also have shown that Humulus japonicus possesses anti-inflammatory activities and may significantly improve antioxidant potential in Raw 264.7 macrophage cells. Thus, the aim of this study was evaluated the effect of Humulus japonicus extract on sperm motility and subsequent preimplantation developmental competence of the bovine embryos. After in vitro maturation, the oocytes with sperms were exposed in in vitro fertilization (IVF) medium supplemented with Humulus japonicus extract (0.01, 0.05, $0.1{\mu}g/mL$, respectively) for 1 day. In our results, exposure of IVF medium to Humulus japonicus extract did not affect sperm motility and percentage of penetrated oocytes but ROS intensity was significantly decreased by $0.01{\mu}g/mL$ compared with other groups (p< 0.05). Moreover, treatment with $0.01{\mu}g/mL$ of Humulus japonicus extract was higher the frequency of blastocyst formation than the any other groups (p<0.05). Otherwise, treatment with $0.01{\mu}g/mL$ of Humulus japonicus extract not increased the total cell number but reduced apoptotic-positive nuclei number. In conclusion, our results indicate that supplementation of Humulus japonicus extract in IVF medium may have important implications for improving early embryonic development in bovine embryos.

• Journal of Pharmacopuncture
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• v.19 no.1
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• pp.37-44
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• 2016

Objectives: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide-co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.