• Journal of Ginseng Research
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• v.43 no.2
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• pp.172-178
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• 2019

Inflammation is an innate immune response that protects the body from pathogens, toxins, and other dangers and is initiated by recognizing pathogen-associated molecular patterns or danger-associated molecular patterns by pattern-recognition receptors expressing on or in immune cells. Intracellular pattern-recognition receptors, including nucleotide-binding oligomerization domain-like receptors (NLRs), absent in melanoma 2, and cysteine aspartate-specific protease (caspase)-4/5/11 recognize various pathogen-associated molecular patterns and danger-associated molecular patterns and assemble protein complexes called "inflammasomes." These complexes induce inflammatory responses by activating a downstream effector, caspase-1, leading to gasdermin D-mediated pyroptosis and the secretion of proinflammatory cytokines, such as interleukin $(IL)-1{\beta}$ and IL-18. Ginsenosides are natural steroid glycosides and triterpene saponins found exclusively in the plant genus Panax. Various ginsenosides have been identified, and their abilities to regulate inflammatory responses have been evaluated. These studies have suggested a link between ginsenosides and inflammasome activation in inflammatory responses. Some types of ginsenosides, including Rh1, Rg3, Rb1, compound K, chikusetsu saponin IVa, Rg5, and Rg1, have been clearly demonstrated to inhibit inflammatory responses by suppressing the activation of various inflammasomes, including the NLRP3, NLRP1, and absent in melanoma 2 inflammasomes. Ginsenosides have also been shown to inhibit caspase-1 and to decrease the expression of $IL-1{\beta}$ and IL-18. Given this body of evidence, the functional relationship between ginsenosides and inflammasome activation provides new insight into the understanding of the molecular mechanisms of ginsenoside-mediated antiinflammatory actions. This relationship also has applications regarding the development of antiinflammatory remedies by ginsenoside-mediated targeting of inflammasomes, which could be used to prevent and treat inflammatory diseases.

• Korean Journal of Veterinary Research
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• v.64 no.1
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• pp.2.1-2.8
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• 2024

This study was performed to assess the antiapoptotic effect of canine platelet-rich plasma (PRP) treated on the canine adipose-derived mesenchymal stem cells (cMSCs) under cold ischemic conditions. The effect of preventing apoptosis of cMSCs was evaluated in the apoptotic condition induced by cold ischemic injury in vitro. To determine the progression of apoptosis, the changes in cell nucleus were observed using 4',6-diamidino-2-phenylindole (DAPI) fluorescence staining. In addition, we examined the mitochondrial membrane potential (MMP) and caspase-3 activity. When the cold hypoxic injury was applied to cMSCs, the apoptotic change was observed by DAPI staining, mitochondrial staining for MMP, and caspase-3 assay. PRP significantly decreased the number of apoptotic cells. Nuclear shrinkage and fragmentation of apoptotic cells in control groups were observed by DAPI staining. The MMP was recovered by the treatment of PRP. In addition, when the luminescence intensity was measured for caspase-3 activity, the value was significantly higher in the PRP treated groups than the control groups. The results of this study showed that the PRP may have a beneficial effect on apoptosis induced by cold ischemic injury.

• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.240-248
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• 2024

In cancer treatment, multi-target approach has paid attention to a reasonable strategy for the potential agents. We investigated whether (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) could exert an anticancer effect by dual-regulating VEGFR2 and PPARγ. MMPP showed modulating effects in TNBC type (MDA-MB-231 and MDA-MB-468) and luminal A type (MCF7) breast cancer cell lines. MMPP enhanced PPARγ transcriptional activity and inhibited VEGFR2 phosphorylation. MMPP-induced signaling by VEGFR2 and PPARγ ultimately triggered the downregulation of AKT activity. MMPP exhibited anticancer effects, as evidenced by growth inhibition, inducement of apoptosis, and suppression of migration and invasion. At the molecular level, MMPP activated pro-apoptotic proteins (caspase3, caspase8, caspase9, and bax), while inhibiting the anti-apoptotic proteins (bcl2). Additionally, MMPP inhibited the mRNA expressions of EMT-promoting transcription factors. Therefore, our findings showed molecular mechanisms of MMPP by regulating VEGFR2 and PPARγ, and suggested that MMPP has potential to treat breast cancer.

• International Journal of Molecular Medicine
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• v.43 no.5
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• pp.2252-2258
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• 2019

Thymic stromal lymphopoietin (TSLP) plays an important role in allergic disorders, including atopic dermatitis and asthma. Ursolic acid (UA) has various pharmacological properties, such as antioxidant, anti-inflammatory and anticancer. However, the effect of UA on TSLP regulation has not been fully elucidated. The aim of the present study was to analyze how UA regulates the production of TSLP in the human mast cell line HMC-1. Enzyme-linked immunosorbent assay, quantitative polymerase chain reaction analysis, western blotting, caspase-1 assay and fluorescent measurements of intracellular calcium levels were conducted to analyze the regulatory effects of UA. The results revealed that UA inhibited TSLP production and mRNA expression. In addition, UA reduced the activation of nuclear factor-κB and degradation of IκBα. Caspase-1 activity was increased by exposure to phorbol myristate acetate plus calcium ionophore, whereas it was reduced by UA. Finally, UA treatment prevented an increase in intracellular calcium levels. These results indicated that UA may be a useful agent for the treatment and/or prevention of atopic and inflammatory diseases, and its effects are likely mediated by TSLP downregulation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.765-771
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• 2005

This study was performed to investigate the anti cancer effect of Batryticatus Bombycis extract(BBE) in B16F10 cells. The cell viability after BBE treatment was quantified by MTT assay. The results showed that BBE inhibited the proliferation of B16F10 cells and caused a 80% inhibition of B16F10 cells at concentration of $500\;{\mu}g/ml$. B16F10 cells exposed to BBE displayed the DNA fragmentation ladder and nucleus chromatin condensation characteristic for apoptosis. The enzyme activity of caspase-3 and actived caspase-3 protein was markedly increased in B16F10 cells treated with the BBE. The expression of Bcl-2, anti-apoptotic protein, was decreased by treatment of the BBE in a dose-dependent manner. And the expression of pro-apoptotic Bax protein was increased. In conclusion, we can suggest that BBE induce the apoptotic death of B16F10 cells via activation of caspase-3, cleavage of PARP protein and Bcl-2 degradation.

• Journal of Preventive Medicine and Public Health
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• v.39 no.3
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• pp.199-204
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• 2006

Objectives: Mercury is a hazardous organ-specific environmental contaminant. It exists in a wide variety of physical and chemical states, each of which has unique characteristics for the target organ specificity. Exposure to mercury vapor and to organic mercury compounds specifically affects the CNS, while the kidney is the target organ for inorganic Hg compounds. Methods: In this study, mercury chloride $(HgCl_2)$ was studied in a renal derived cell system, i.e., the tubular epithelial Madin-Darby canine kidney (MDCK) cell line, which has specific sensitivity to the toxic effect of mercury. MDCK cells were cultured for 6-24 hr in vitro in various concentrations (0.1-100 M) of $HgCl_2$, and the markers of apoptosis or cell death were assayed, including DNA fragmentation, caspase-3 activity andwestern blotting of cytochrome c. The influence of the metal on cell proliferation and viability were evaluated by the conventional MTT test. Results: The cell viability was decreased in a time and concentration dependent fashion: decreases were noted at 6, 12 and 24 hr after $HgCl_2$, exposure. The increases of DNA fragmentation were also observed in the concentrations from 0.1 to 10 M of $HgCl_2$ at 6 hr after exposure. However, we could not observe DNA fragmentation in the concentrations more than 25 M because the cells rapidly proceeded to necrotic cell death. The activation of caspase-3 was also observed at 6 hr exposure in the $HgCl_2$ concentrations from 0.1 to 10 M. The release of cytochrome c from the mitochondria into the cytosol, which is an initiator of the activation of the caspase cascade, was also observed in the $HgCl_2-treated$ MDCK cells. Conclusions: These results suggest that the activation of caspase-3 was involved in $HgCl_2-induced$ apoptosis. The release of cytochrome c from the mitochondria into the cytosol was also observed in the $HgCl_2-treated$ MDCK cells. These findings indicate that in MDCK cells, $HgCl_2$ is a potent inducer of apoptosis via cytochrome c release from the mitochondria.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.465-474
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• 2017

The aim of this study was to determine the raising anticancer effects of resveratrol (Res) on paclitaxel (PA) in non-small cell lung cancer (NSCLC) cell line A549. The $10{\mu}g/ml$ of Res had no effect on human fetal lung fibroblast MRC-5 cells or on A549 cancer cells and the 5 or $10{\mu}g/ml$ of PA also had no effect on MRC-5 normal cells. PA-L ($5{\mu}g/ml$) and PA-H ($10{\mu}g/ml$) had the growth inhibitory effects in NSCLC cell line A549, and Res increased these growth inhibitory effects. By flow cytometry experiment, after Res ($5{\mu}g/ml$)+PA-H ($10{\mu}g/ml$) treatment, the A549 cells showed the most apoptosic cells compared to other group treatments, and after additional treatment with Res, the apoptosic cells of both two PA concentrations were raised. Res+PA could reduce the mRNA and protein expressions of COX-2, and Res+PA could reduce the COX-2 related genes of VEGF, MMP-1, MMP-2, MMP-9, $NF-{\kappa}B$, Bcl-2, BclxL, procollagen I, collagen I, collagen III and CTGF, $TNF-{\alpha}$, $IL-1{\beta}$, iNOS and raise the TIMP-1, TIMP-2, TIMP-3, $I{\kappa}B-{\alpha}$, p53, p21, caspase-3, caspase-8, caspase-9, Bax genes compared to the control cells and the PA treated cells. From these results, it can be suggested that Res could raise the anticancer effects of PA in A549 cells, thus Res might be used as a good sensitizing agent for PA.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.184-189
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• 2008

The proto-oncogene protein DEK has been implicated in various human disease including cancer. We have shown that DEK induces caspase-dependent apoptosis in Drosophila by regulating histone acetylation. Reverse transcription-polymerase chain reaction (RT-PCR) method based on annealing control primers was used to screen and identify differentially expressed genes (DEGs) in DEK overexpressed HeLa cells. Among the genes identified, clusterin and fibrillarin have major role in apoptosis pathway regulation. TFIIIC and RPS24 are implicated in HAT mediated transcriptional initiation and cololectal cancer, respectively. To further analyze DEK's role in apoptosis, multiplex PCR was performed. Caspase-3, -7, and -10 and proapoptotic gene bid were newly identified as possible target genes regulated by DEK expression.

• Journal of Microbiology and Biotechnology
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• v.19 no.8
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• pp.787-791
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• 2009

In the course of screening for substances that inhibit etoposide (10 ${\mu}g$/ml)-induced apoptosis in human leukemia U937 cells, fungal strain F000120, which exhibits potent inhibitory activity, was selected. The active compound was purified from an ethyl acetate extract of the microorganism by Sep-pak $C_{18}$ column chromatography and HPLC, and was identified as heptelidic acid (koningic acid) by spectroscopic methods. This compound inhibited caspase-3 induction in U937 cells with an $IC_{50}$ value of 40 ${\mu}M$ after 8 h of etoposide treatment. Fluorescent dye staining with acridine orange and ethidium bromide showed that heptelidic acid inhibited apoptosis. Furthermore, it was found that DNA fragmentation and caspase-3 activation, the biological hallmarks of apoptosis, were inhibited by the compound in a dose-dependent manner, suggesting that heptelidic acid inhibits etoposide-induced apoptosis via downregulation of caspases.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.891-894
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• 2013

The present study was performed to assess the activity of the botulinum toxin A on breast cancer cells. The T47D cell line was exposed to diverse concentrations of the botulinum toxin A and cell viability and apoptosis were estimated using MTT and propidium iodine/annexin V methods, respectively. Botulinum toxin A exerted greater cytotoxic activity in T47D cells in comparison with MCF10A normal cells; this appeared to be via apoptotic processes caspase-3 and -7. In conclusion, botulinum toxin A induces caspase-3 and -7 dependent apoptotic processes in the T47D breast cancer cell line.