• Clinical and Experimental Pediatrics
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• v.46 no.7
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• pp.679-686
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• 2003

Purpose : Ataxia telangiectasia mutated(ATM) is involved in DNA damage responses at different cell cycle checkpoints, and signalling pathways associated with regulation of apoptosis in response to ionizing radiation(IR). However, the signaling pathway that underlies IR-induced apoptosis in ATM cells has remained unknown. The purpose of this study was, therefore, to investigate the apoptotic pathway that underlies IR-induced apoptosis in a CT-26 cells expressing dominant negative ATM (DN-ATM). Methods : We generated a replication-deficient recombinant adenovirus encoding the DN-ATM(Ad/DN-ATM) or control adenovirus encoding no transgene(Ad/GFP) and infected adenovirus to CT-26 cells. After infection, we examined apoptosis and apoptotic pathway by [$^3H$]-thymidine assay, DNA fragmentation, and Western immunoblot analysis. Results : DN-ATM gene served as the creation of AT phenotype in a CT-26 cells as revealed by decreased cell proliferations following IR. In addition, IR-induced apoptosis was regulated through the reduced levels of the anti-apoptotic protein Bcl-2, the increased levels of the apoptotic protein Bax, and the activation of caspase-9, caspase-3, and PARP. Conclusion : These results indicate that the pathway of IR-induced apoptosis in CT-26 cells expressing DN-ATM is mediated by mitochondrial signaling pathway involving the activation of caspase 9, caspase 3, and PARP.

• Parasites, Hosts and Diseases
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• v.44 no.3
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• pp.233-237
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• 2006

We postulated that apolysis was processed in accordance with apoptotic changes occurring in a cestode, Spirometra erinacei (Pseudophyllidea). We cloned the novel putative apoptosis-associated gene from S. erinacei via screening of a S. erinacei cDNA library with a ced-3 gene (activator of apoptosis) probe from Caenorhabditis elegans. We identified a 261-bp cDNA sequence, which encodes for an 86-amino acid protein. The cloned gene expression was observed in the neck and gravid proglottids via Northern blotting, using cloned cDNA inserts as probes, but the clone was not expressed in any of other tissues. We suggest that this gene may be involved in the apolysis of S. erinacei during normal tissue development and differentiation in cestode parasites.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.386-391
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• 2017

Background: Korean Red Ginseng (KRG) is an ethnopharmacological plant that is traditionally used to improve the body's immune functions and ameliorate the symptoms of various diseases. However, the antitumorigenic effects of KRG and its underlying molecular and cellular mechanisms are not fully understood in terms of its individual components. In this study, in vitro and in vivo antitumorigenic activities of KRG were explored in water extract (WE), saponin fraction (SF), and nonsaponin fraction (NSF). Methods: In vitro antitumorigenic activities of WE, SF, and NSF of KRG were investigated in the C6 glioma cell line using cytotoxicity, migration, and proliferation assays. The underlying molecular mechanisms of KRG fractions were determined by examining the signaling cascades of apoptotic cell death by semiquantitative reverse transcriptase polymerase chain reaction and Western blot analysis. The in vivo antitumorigenic activities of WE, SF, and NSF were investigated in a xenograft mouse model. Results: SF induced apoptotic death of C6 glioma cells and suppressed migration and proliferation of C6 glioma cells, whereas WE and NSF neither induced apoptosis nor suppressed migration of C6 glioma cells. SF downregulated the expression of the anti-apoptotic gene B-cell lymphoma-2 (Bcl-2) and upregulated the expression of the pro-apoptotic gene Bcl-2-associated X protein (BAX) in C6 glioma cells but had no effect on the expression of the p53 tumor-suppressor gene. Moreover, SF treatment resulted in activation of caspase-3 as evidenced by increased levels of cleaved caspase-3. Finally, WE, SF, and NSF exhibited in vivo antitumorigenic activities in the xenograft mouse model by suppressing the growth of grafted CT-26 carcinoma cells without decreasing the animal body weight. Conclusion: These results suggest that WE, SF, and NSF of KRG are able to suppress tumor growth via different molecular and cellular mechanisms, including induction of apoptosis and activation of immune cells.

• Journal of Ginseng Research
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• v.36 no.1
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• pp.68-77
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• 2012

In this study, we investigated the protective effects of processed Panax ginseng, sun ginseng (SG) against the UVB-irradiation on epidermal keratinocytes and dermal fibroblasts. Pretreatment of SG in HaCaT keratinocytes and human dermal fibroblasts reduced UVB-induced cell damage as seen by reduced lactate dehydrogenase release. We also found that SG restored the UVB-induced decrease in anti-apoptotic gene expression (bcl-2 and bcl-xL) in these cells, indicating that SG has an anti-apoptotic effect and thus can protect cells from cell death caused by strong UVB radiation. In addition, SG inhibited the excessive expression of c-jun and c-fos gene by the UVB in HeCaT cells and human dermal fibroblasts. We also demonstrated that SG may exert an anti-inflammatory activity by reducing the nitric oxide production and inducible nitric oxide synthase mRNA synthesis in HaCaT keratinocytes and human dermal fibroblasts. This was further supported by its inhibitory effects on the elevated cyclooxygenase-2 and tumor necrosis factor-${\alpha}$ transcription which was induced by UVB-irradiation in HaCaT cells. In addition, SG may have anti-aging property in terms of induction of procollagen gene expression and inhibition of the matrix metalloprotease-1 gene expression caused by UVB-exposure. These findings suggest that SG can be a potential agent that may protect against the dermal cell damage caused by UVB.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2004.11a
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• pp.53-60
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• 2004

The pro-apoptotic effect of phenethyl isothiocyanate (PEITC) and the role of glutathione (GSH) in sulforaphane (SFN)-induced antioxidant response element-dependent gene expression were investigated. The caspase-3 and caspase-9 activities were stimulated by PEITC. The release of cytochrome c was time- and dose- dependent. SP600125 suppressed apoptosis induced by PEITC. Similarly, this JNK inhibitor attenuated both cytochrome c release and caspase-3 activation induced by PEITC. SFN is converted to the glutathione conjugate by glutathione S-transferases (GSTs). It was accumulated in mammalian cells by up to several hundred-fold over the extracellular concentration, by conjugation with intracellular GSH. The induction of ARE by SFN was 8.6-fold higher than by SFN-NAC. The decrease in ARE expression at higher concentrations of SFN and SFN-NAC was correlated with the accelerated apoptotic cell death, with a dose-dependent activation of caspase 3 activity by SFN. Upon addition of extracellular GSH within 6 hr of treatment with SFN, the effect on ARE expression was blocked almost completely.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1102-1106
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• 2004

To investigate the anti-proliferative effects of an aqueous extract of Cordyceps militaris (AECM) on the growth of human lung carcinoma cell line A549, we performed various biochemical experiments such as the effects of AECM on the cell proliferation and viability, the morphological changes, the effects on expression of apoptosis and cell growth-regulatory gene products. Results obtained are as follow; AECM treatment declined the cell viability and proliferation of A549 cells in a concentration-dependent manner. The anti-proliferative effect by AECM treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. Taken together, these findings suggest that AECM-induced inhibition of human lung cancer cell proliferation is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and C. militaris may have therapeutic potential in human lung cancer.

• BMB Reports
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• v.40 no.6
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• pp.966-972
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• 2007

Pituitary tumor transforming gene (PTTG1) is widely detected in many tumors. Increasing evidence reveals that PTTG1 is associated with cell proliferation, cellular transformation and apoptosis. However, the functions of PTTG1, especially its role in DNA damage-induced apoptosis, remain largely unclear. In this report, we used UV irradiation to induce apoptosis in HeLa cells to examine the role of PTTG1 in UV-induced apoptosis by RNAi-mediated knockdown and overexpression of PTTG1. RNAi-mediated knockdown of PTTG1 expression increased and overexpression of PTTG1 decreased the UV-induced apoptosis. Furthermore, UV irradiation decreased PTTG1 mRNA and protein expression. These effects were found to be mediated by JNK pathway. Therefore, PTTG1 had an important anti-apoptotic role in UV-induced apoptosis and this role was mediated by JNK pathway. These results may provide important information for understanding the exact role and the regulation mechanism of PTTG1 in UV-induced apoptosis.

• Reproductive and Developmental Biology
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• v.37 no.4
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• pp.175-183
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• 2013

Cathepsin B is abundantly expressed peptidase of the papain family in the lysosomes, and closely related to the cell degradation system such as apoptosis, necrosis and autophagy. Abnormal degradation of organelles often occurs due to release of cathepsin B into the cytoplasm. Many studies have been reported that relationship between cathepsin B and intracellular mechanisms in various cell types, but porcine embryos has not yet been reported. Therefore, this study evaluated the effect of cathepsin B inhibitor (E-64) on preimplantation developmental competence and quality of porcine embryos focusing on apoptosis and oxidative stress. The expression of cathepsin B mRNA in porcine embryos was gradually decreased in inverse proportion to E-64 concentration by using real-time RT-PCR. When putative zygotes were cultured with E-64 for 24 h, the rates of early cleavage and blastocyst development were decreased by increasing E-64 concentration. However, the rate of blastocyst development in $5{\mu}M$ treated group was similar to the control. On the other hand, both the index of apoptotic and reactive oxygen species (ROS) of blastocysts were significantly decreased in the $5{\mu}M$ E-64 treated group compared with control. We also examined the mRNA expression levels of apoptosis related genes in the blastocysts derived from $5{\mu}M$ E-64 treated and non-treated groups. Expression of the pro-apoptotic Bax gene was shown to be decreased in the E-64 treated blastocyst group, whereas expression of the anti-apoptotic Bcl-xL gene was increased. Taken together, these results suggest that proper inhibition of cathepsin B at early development stage embryos improves the quality of blastocysts, which may be related to not only the apoptosis reduction but also the oxidative stress reduction in porcine embryos.

• Korean Journal of Medicinal Crop Science
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• v.23 no.2
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• pp.138-143
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• 2015

This study was carried out to evaluate the preventive effect of three forms of Korean ginseng roots (fresh, white and red) against bisphenol A (BPA) toxicity in mouse male germ cells (GC-2spd, TM3, TM4). ROS (reactive oxygen species) generation were measured by DCF-DA (2',7'-dichlorohydrofluorescein diacetate) assay. Also, semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was performed to quantify the mRNA expression levels of apoptosis-related genes, Bax (pro-apoptotic gene) and Bcl2 (anti-apoptotic gene). ROS generation was increased by $50{\mu}M$ BPA, but definitely decreased by treatment with Korean ginseng extracts (fresh, white and red) in mouse male germ cells. In especial, Korean fresh ginseng extract reduced significantly ROS production to normal control. In addition, Korean fresh and white ginseng extracts suppressed the apoptosis of mouse male germ cells by fine-tuning mRNA levels of apoptotic genes changed by BPA. In general, Korean fresh ginseng extract was more effective than white ginseng extract for reducing BPA-induced oxidative stress and apoptosis in mouse male germ cells. Therefore, Korean fresh and white ginseng may help to alleviate biphenol A toxicity in mouse male germ cells.

• Journal of the Korean Society of Food Culture
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• v.36 no.2
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• pp.235-245
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• 2021

Lindera glauca Blume has been used in Korean traditional medicine to treat the symptoms of paralysis, abdominal pain, speech disorders, extravasations, contusions, and pain caused by rheumatoid arthritis. We investigated the effect of L. glauca Blume extracts on the proliferation of colorectal cancer cells in vitro using HCT116 human colorectal cancer cell lines. We also investigated its mechanism of action. For this purpose, we used the MTT assay, western blotting, DNA fragmentation analysis, and flow cytometry. HCT116 cells were cultured in several concentrations of ethanol extracts of L. glauca Blume root (0, 50, 100 ㎍/mL). In this study, colon cancer cell growth was inhibited by L. glauca Blume root extract in a dose-dependent manner. It was associated with induction of apoptosis as assessed by nuclear fragmentation and cell cycle analysis. Apoptosis was assessed using western blotting for TNF-α, IL-6, NF-κB, Caspase-3, PARP, Bax, Bcl-2, and SIRT1. The extract also dose-dependently upregulated the expression Bax, the pro-apoptotic gene and downregulated the expression of the anti-apoptotic gene Bcl-2. Furthermore, the extract enhanced Caspase-3 activity in a dose-dependent manner. Our findings provide evidence that L. glauca Blume extract may mediate its anti-proliferative effect via the modulation of apoptosis.