• Journal of Nutrition and Health
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• v.36 no.8
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• pp.828-833
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• 2003

Dially disulfide (DADS), a component of garlic (Allium sativum), has been known to exert potent chemopreventive activity against various cancers. In this study, the synergistic effect of DADS and daunorubicin on the cytotoxicity of HL-60 cells, a human leukemia cell line, was investigated. DADS at 25 M greatly potentiated daunorubicin-induced cell death, decreasing cell viabilityto50%ofthe control. Daunorubicin-induced apoptosis was accompanied by the activation of caspase-3, the degradation of poly-(ADP-ribose) polymerase (PARP) and D4-GDI, and DNA fragmentation, which were blocked by pre-treatment with acetyl-Asp-Glu-Val-Asp- dialdehyde (Ac-DEVD-CHO). Treatment that combined 25 M DADS and 100 nM daunorubicin caused a similar degree of caspase-3 activation, PARP and D4-GDI degradation, and DNA fragmentation to that caused by treatment with 250 nM daunorubicin alone. These results indicate that combined therapy using daunorubicin with DADS, a component of food, and garlic can effectively decrease the therapeutic dose of daunorubicin, preventing the severe side effects of daunorubicin.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.1
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• pp.257-266
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• 2008

Purpose: These experiments were undertaken to evaluate the effect of Onpoeum on ovarian functions and differential gene expressions related with cell viabilities caspase-3, MAPK and MPG in female mice. Methods: We administered the Onpoeum to 6-week-old female ICR mice for 4, 8, or 12 days. With different concentration of Onpoeum, the female mice were injected PMSG and hCG for ovarian hyperstimulation. The mice divided into 3 different groups for each experiment. We chose the Caspase-3 for cell apoptosis, MAPK and MPG genes for cell viability and DNA repair. Results: In case of 4, 8, 12 day of Onpoeum, we were examined the mean number of total ovulated oocytes and the number of morphologically normal oocytes. We were also examined the embryonic developmental competence in vitro. In addition we were examined the differential expression of cell apoptosis, viability and DNA repair related genes, Caspase-3, MAPK and MPG according to concentration and duration of Onpoeum. From these results showed that the administration of Onpoeum played a role of prevention of cell apoptosis and DNA damages and also increased cell proliferation resulted in ovarian functions. Conclusions: It is suggested that the medication of Onpoeum may have beneficial effect on reproductive functions of female mice via prevention of cell apoptosis and DNA damaging and promotion of cell proliferation.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1887-1890
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• 2016

Breast cancer is the most common cause of cancer-related death among women in the whole world. MiR- 34a and let-7a are well known tumor suppressors that participate in the regulation of apoptosis, invasion and other cellular functions. In this study, expression of miR-34a, let-7a and apoptosis pathway genes such as Bcl-2, Caspase-3 and P53 were evaluated using quantitative real-time PCR in 45 paired samples of normal margin and tumor tissue collected from breast cancer patient at advanced stage (3-4). MiR-34a, let-7a, caspase-3 and P53 expression are reduced and Bcl-2 expression is increased within tumoral tissues in comparison with normal margin tissues. P53 expression directly or indirectly was correlated with miR-34a, let-7a, Bcl-2 and caspase-3 expression. In This study we found that MiR-34a and let-7a expression are reduced in the tumoral tissues. Down-regulation of these two molecules correlated with expression of genes associated with apoptosis. These results suggest that due to the correlation of miR-34a and let-7a with apoptotic and anti-apoptotic pathways these molecules could participate as regulators in advanced clinical stages of breast cancer and should be considered as markers for diagnosis, prognostic assessment and targeted therapy.

• Biomedical Science Letters
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• v.20 no.4
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• pp.244-249
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• 2014

Arazyme is a metalloprotease secreted by Aranicola proteolyticus that was previously shown to suppress cytokine expression of keratinocytes and endothelial cells and inhibit histopathological features in an atopic dermatitis-like animal model. However, the regulatory effects of arazyme in other allergic diseases have yet to be elucidated. In this study, we investigated whether arazyme is effective against neutrophil apoptosis in allergic diseases such as allergic rhinitis and asthma. Arazyme inhibited neutrophil apoptosis of normal subjects in a dose-dependent manner. However, the antiapoptotic effect of arazyme was reversed by LY294002, an inhibitor of PI3K, AKTi, an inhibitor of Akt, PD98059, an inhibitor of MEK, and BAY-11-7085, an inhibitor of NF-${\kappa}B$. Arazyme induced activation of NF-${\kappa}B$ via PI3K/Akt/ERK pathway. The anti-apoptotic effect of arazyme is associated with inhibition of cleavage of caspase 3 and caspase 9. Arazyme inhibited constitutive apoptosis of neutrophil in a dose-dependent manner in allergic subjects, and its mechanism was shown to be associated with PI3K/Akt/ERK/NF-${\kappa}B$. The results presented here improve our understanding of neutrophil apoptosis regulation and will facilitate development of drugs for treatment of allergic diseases.

• Korean Journal of Environmental Biology
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• v.27 no.1
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• pp.66-72
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• 2009

Diabetic Retinopathy (DR) is a leading cause of blindness among adults in the western countries. Hyperglycemia is a condition, that induces apoptotic cell death in a variety of cell types in diabetes, but the mechanism remains unclear. The aim of the study is to understand the effects of high Glucose on Human Retinal Endothelial Cells. Retinal endothelial cells were cultured in Iscove's Modified Dulbecco's Medium (IMDM) containing 5, 25 and 50 mM Glucose, incubated for 24, 36 and 48 hours in humidified 5 % CO$_2$ incubator at 37$^{\circ}C$. Human Retinal Endothelial Cell Line (HREC) were characterized for morphology with different treatment by phase contrast microscopic analysis. Number of dead and viable cells was counted by trypan blue exclusion and supported by MTT assay. The intracellular Hydrogen peroxide (H$_2$O$_2$), a Reactive Oxygen Species (ROS) generation in high glucose conditions was assessed by FOX II assay and apoptosis by caspase-3 assay. The high glucose treated cells undergoing DNA fragmentation was witnessed by Agarose gel electrophoresis. We found that the cells incubated with 25 and 50 mM glucose containing medium for 48 hours altered the morphology of the cell, induced apoptosis and DNA fragmentation. The dead cell number were high in 25 and 50 mM when compared to the cells incubated with 5 mM glucose for 24, 36, and 48 hours. Also, the H$_2$O$_2$ levels and the activity of caspase-3 were increased in high glucose treated cells. Conclusions/interpretation: Our results demonstrated that elevated glucose induces apoptosis in cultured HREC. The hyperglycemia-induced increase in apoptosis may be dependent on caspase activation. The association between ROS generation and caspase-3 activation on high glucose treated cells is yet to be investigated.

• Physical Therapy Korea
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• v.11 no.2
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• pp.47-63
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• 2004

In most tissues, apoptosis plays a pivotal role in normal development and in regulation of cell number. Therefore inappropriate apoptosis is revealed in a variety of diseases. This study was carried out to investigate the effects of acupuncture and needle electrode electrical stimulation on the change of caspase-3, 9 and neuronal nitric oxide synthase (nNOS) immunoreactive cells in the sprague dawley rats (SD rat). In immobilized SD rats (n=5), enhanced caspase-3 and caspase-9 expression were detected in the reticular part of substantia nigra, and enhanced nNOS was detected in the dorsolateral periaqueductal gray (DL-PAG) of midbrain and the paraventricular nucleus (PVN) of the hypothalamus using immunohistochemistry. Following the immobilization, acupuncture (n=5) and needle electrode electrical stimulation (n=5, 2 Hz) was applied at H$\acute{e}$g$\breve{u}$ (LI4) acupoint of SD rats, respectively. The stress-induced enhancement in the expression of caspase-3, 9 and nNOS were The present results demonstrate that and needle electrode electrical stimulation are effective in the modulation of expression of caspase-3, 9 and nNOS induced by immobilization.

• The Journal of Korean Obstetrics and Gynecology
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• v.20 no.3
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• pp.91-110
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• 2007

Purpose : These experiments were undertaken to evaluate the effect of administration of Palmultang on ovarian functions and differential gene expressions related cell viabilities caspase-3, MAPK and MPG in female mice. Materials and Methods : We administered the Palmultang to 6-week-old female ICR mice for 4, 8, or 12 days. The female mice were injected PMSG and hCG for ovarian hyperstimulation. And then recovered ovaries were minced and extracted mRNA and analyzed cell viability related gene expression. We chose the caspase-3 for cell apoptosis, MAPK and MPG genes for cell viability and DNA repair. To compare the differences, we set a control group treated with plain water at the same volume by the same way. Results : In case of administration of Palmultang, the mean number of total ovulated oocytes and the number of morphologically normal oocytes increased significantly compared to a control group. We were also examined the embryonic developmental competence in vitro. The administration of Palmultang in a concentration with 10 and 100 mg/ml were beneficial effect of embryonic development in preimplantation period. The administration of Palmultang play a role of prevention of cell apoptosis and DNA damages and also increased cell proliferation resulted in ovarian functions. Conclusion : From our results suggested that the medication of Palmultang has beneficial effect on reproductive functions of female mice via prevention of cell apoptosis and DNA damaging and promotion of cell proliferation.

• Journal of Life Science
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• v.17 no.4 s.84
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• pp.552-560
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• 2007

Histone deacetylase (HDAC) is overexpressed in a variety of cancers and is closely correlated with oncogenic factors. HDAC inhibitors such as trichostatin A(TSA) and sodium butyrate (Na-B) have been shown to induce apoptosis in vitro and in vivo in many cancer cells. The anti-apoptotic Bcl-2 protein has the remarkable ability to prevent cell death and Bcl-2 overexpression has been reported to protect against cell death. We previously reported that the apoptotic cell death of human leukemic U937 cells by TSA and Na-B treatment was associated with the down-regulation of Bcl-2 expression and activation of caspases. In the present study, we investigated the effects of Bcl-2 overexpression on the growth inhibition, cell cycle arrest and apoptosis induced by TSA and Na-B in U937 cells. TSA-induced growth inhibition, cell cycle arrest and apoptosis were significantly attenuated in Bcl-2 overexpressing U937/Bcl-2 cells however Na-B did not affected. Induction of apoptosis by TSA was accompanied by down-regulation of Bcl-2 expression, activation of caspase-3, -8 and -9, and degradation of DNA fragmentation factor/inhibitor of caspase-activated DNase, which was blocked by the overexpression of Bcl-2. Collectively, these findings suggest that ectopic expression of Bcl-2 appeared to inhibit TSA-induced apoptosis by interfering with inhibition of Bcl-2 and caspase activation.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1771-1779
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• 2015

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Presently, targeted therapy via monoclonal antibodies to specific tumor-associated antigens is being continuously developed. Hep88 mAb has proven to exert tumoricidal effects on the HepG2 cell via a paraptosis-like morphology. To verify the pathway, we then demonstrated downstream up-regulation of caspase-3, caspase-8 and caspase-9, assessingmRNA expression by real-time PCR and associated enzyme activity by colorimetric assay. Active caspase-3 determination was also accomplished by flow cytometry. Active caspase-3 expression was increased by Hep88 mAb treatment in a dose-and time-dependent manner. All of the results indicated that Hep88 mAb induced programmed cell death in the HepG2 cell line from paraptosis-like to apoptosis by downstream induction of caspases. These conclusions imply that Hep88mAb might be a promising tool for the effective treatment of HCC in the future.

• Journal of Microbiology and Biotechnology
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• v.31 no.6
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• pp.794-802
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• 2021

In this study we investigated the role and mechanism of cardamonin on IL-1β induced injury in OA. CHON-001 cells were treated with cardamonin and IL-1β and transfected with silencing nuclear factor erythroid 2-related factor 2 (siNrf2). Cell viability was detected by Cell Counting Kit-8 assay and flow cytometer assay was utilized for cell apoptosis assessment. IL-6, IL-8, TNF-α and Nrf2 mRNA expression was tested by qRT-PCR. Western blot was employed to evaluate MMP-3, MMP-13, Collagen II, Nrf2, NQO-1, NLRP3, Caspase 1 and apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) protein levels. In CHON-001 cells, IL-1β suppressed cell viability and Collagen II level while promoting cell apoptosis and expression of pro-inflammatory cytokines (IL-6, IL-8, TNF-α), MMPs (MMP-3, MMP-13), NQO-1, and NLRP3 inflammasome (NLRP3, Caspase 1 and ASC), with no significant influence on Nrf2. Cardamonin reversed the effect of IL-1β on cell viability, cell apoptosis, pro-inflammatory cytokines, MMPs, Collagen II, and NLRP3 inflammasome levels. In addition, cardamonin advanced Nrf2 and NQO-1 expression of CHON-001 cells. SiNrf2 reversed the function of cardamonin on IL-1β-induced cell apoptosis and expression of pro-inflammatory cytokines, Nrf2, NQO-1, and NLRP3 inflammasome in chondrocytes. Taken together Cardamonin inhibited IL-1β induced injury by inhibition of NLRP3 inflammasome via activating Nrf2/NQO1 signaling pathway in chondrocyte.