• Reproductive and Developmental Biology
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• 제35권2호
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• pp.167-174
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• 2011

Acute ischemic stroke results from sudden decrease or loss of blood supply to an area of the brain, resulting in a coinciding loss of neurological function. The antioxidant action of melatonin is an important mechanism among its known effects to protective activity during ischemic/reperfusion injury. The focus of this research, therapeutic efficacy of melatonin on recovery of neurological function following long term treatment in ischemic brain injured rats. Male Sprague-Dawley rats (n=40; 8 weeks old) were divided into the control group, and MCAo groups (Vehicle, MT7 : MCAo+ melatonin injection at 7:00, MT19 : MCAo+melatonin injection at 19:00, and MT7,19 : MCAo+melatonin injection at 7:00 and 19:00). Rat body weight and neurological function were measured every week for 8 weeks. After 8 weeks, the rats were anesthetized with a mixture of zoletil (40 mg/kg) and xylazine (10 mg/kg) and sacrificed for further analysis. Tissues were then collected for RNA isolation from brain tissue. Also, brain tissues were analyzed by histological procedures. We elucidated that melatonin was not toxic in vital organs. MT7,19 was the most rapidly got back to mild symptom on test of neurological parameter. Also, exogenous melatonin induces both the down-regulation of detrimental genes, such as NOSs and the up-regulation of beneficial gene, including BDNF during long term administration after focal cerebral ischemia. Melatonin treatment reduced the loss of primary motor cortex. Therefore, we suggest that melatonin could be act as prophylactic as well as therapeutic agent for neurorehabilitative intervention.

• 대한한방내과학회지
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• 제25권4호
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• pp.274-288
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• 2004

Objectives : This study was designed to evaluate the effect on cytotoxicity of Bojungikki-tang(BIT) in human lung cancer H460 cells. Methods : BIT-induced cell death was confirmed as apoptosis characterized by chromatin condensation and increase of the $sub-G_1$, DNA content. It was tested whether the water extract of BIT affects the cell cycle regulators such as, p2l/Cipl, p27/Kipl, cyclin $B_1$. Results : The data showed that treatment of BIT decreased the viability of H460 cells in a dose-dependent manner. p2l/Cip1 is gradually decreased by the addition of the cells with BIT extract. Interestingly, p27/Kip1 is not detected for 24 hr after the addition of BIT extract, however, after 24 hr, p27/Kipl markedly increased. In addition, cyclin $B_1$, decreased in a time dependent manner after the addition of the water extract. The activation of caspase -3 protease was further confirmed by degradation of procaspase-8 protease andpoly(ADP-ribose) polymerase(P ARP) by BIT in H460 cells. Moreover, BIT induced the increase of Bak expression. Conclusion : These results suggest that the extract of BIT exerts anticancer effects to induce the death of human lung cancer H460 cells via down regulation of cell cycle regulators such as p2l/Cip1, and cyclin B1 or up regulation of cell cycle regulators such as p27/Kip1. Moerover results suggest that BIT induces an apoptosis in H460 cells via activation of intrinsic caspase cascades.

• Biomolecules & Therapeutics
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• 제17권1호
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• pp.17-24
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• 2009

Histone deacetylase (HDAC) inhibitors are a promising class of anticancer agents that inhibit cancer cell growth in vitro and in vivo. Previous report has shown that apicidin inhibited SK-OV-3 cells proliferation and down-regulation of cyclin B1 and CDK1, and up-regulation of $p21^{WAF1}$ and p27. However, the mechanism of apicidin-mediated apoptotic cell death is not clearly understood. For this study, we investigated the mechanism of apoptotic pathway induced by apicidin in human ovarian cancer cell. We found that SK-OV-3 cells treated with apicidin caused an increase in the percentage of cells in the G2/M phase, which preceded apoptosis characterized by the appearance of cells with sub-G1 population. To further investigate the mechanism of apoptosis induction by apicidin, we measured TUNEL assay, poly-ADP ribose polymerase (PARP) cleavage, and caspase activity in SK-OV-3 cells treated with apicidin for 48 h. Apicidin significantly enhanced apoptosis as measured by TUNEL positive apoptotic cells, PARP cleavage, and increased Bax/Bcl-2 ratio. Induction of apoptosis was confirmed by the release of cytochrome c to cytosol. Our data suggest that apicidin-induced apoptosis in SK-OV-3 cells was accompanied by caspase-3 activation and the increase in Bax/Bcl-2 ratio. These data suggest that apicidin may be effective in the treatment of ovarian cancer through activation of intrinsic apoptotic pathway.

• Biomolecules & Therapeutics
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• 제21권4호
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• pp.270-276
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• 2013

Fucoxanthin is an important carotenoid derived from edible brown seaweeds and is used in indigenous herbal medicines. The aim of the present study was to examine the cytoprotective effects of fucoxanthin against hydrogen peroxide-induced cell damage. Fucoxanthin decreased the level of intracellular reactive oxygen species, as assessed by fluorescence spectrometry performed after staining cultured human HaCaT keratinocytes with 2',7'-dichlorodihydrofluorescein diacetate. In addition, electron spin resonance spectrometry showed that fucoxanthin scavenged hydroxyl radical generated by the Fenton reaction in a cell-free system. Fucoxanthin also inhibited comet tail formation and phospho-histone H2A.X expression, suggesting that it prevents hydrogen peroxide-induced cellular DNA damage. Furthermore, the compound reduced the number of apoptotic bodies stained with Hoechst 33342, indicating that it protected keratinocytes against hydrogen peroxide-induced apoptotic cell death. Finally, fucoxanthin prevented the loss of mitochondrial membrane potential. These protective actions were accompanied by the down-regulation of apoptosis-promoting mediators (i.e., B-cell lymphoma-2-associated ${\times}$ protein, caspase-9, and caspase-3) and the up-regulation of an apoptosis inhibitor (B-cell lymphoma-2). Taken together, the results of this study suggest that fucoxanthin defends keratinocytes against oxidative damage by scavenging ROS and inhibiting apoptosis.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.159-160
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• 2001

Gap junctional intercellular communication (GJIC) is a cellular event underlying the tumor promotion process and that treatment to prevent the down-regulation or to up-regulate GJIC is important in preventing tumor promotion. We evaluated the potential preventive effect of Mushroom Phellinus Linteus (PL) against the promoting action of hydrogen peroxide ($H_2O$$_2$) in WB-F344 rat liver epithelial cells.(omitted)

• Biomolecules & Therapeutics
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• 제20권6호
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• pp.513-519
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• 2012

Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the $IC_{50}$ values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.434-441
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• 2015

Histone deacetylase (HDAC) inhibitors are considered novel agents for cancer chemotherapy. We previously investigated MHY219, a new HDAC inhibitor, and its potent anticancer activity in human prostate cancer cells. In the present study, we evaluated MHY219 molecular mechanisms involved in the regulation of prostate cancer cell migration. Similar to suberanilohydroxamic acid (SAHA), MHY219 inhibited HDAC1 enzyme activity in a dose-dependent manner. MHY219 cytotoxicity was higher in LNCaP ($IC_{50}=0.67{\mu}M$) than in DU145 cells ($IC_{50}=1.10{\mu}M$) and PC3 cells ($IC_{50}=5.60{\mu}M$) after 48 h of treatment. MHY219 significantly inhibited the HDAC1 protein levels in LNCaP and DU145 cells at high concentrations. However, inhibitory effects of MHY219 on HDAC proteins levels varied based on the cell type. MHY219 significantly inhibited LNCaP and DU145 cells migration by down-regulation of matrix metalloprotease-1 (MMP-1) and MMP-2 and induction of tissue inhibitor of metalloproteinases-1 (TIMP-1). These results suggest that MHY219 may potentially be used as an anticancer agent to block cancer cell migration through the repression of MMP-1 and MMP-2, which is related to the reduction of HDAC1.

• Food Science and Biotechnology
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• 제16권2호
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• pp.205-211
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• 2007

This study was designed to investigate the suppressive effect of chlorophyll a on nitric oxide (NO) production and intracellular oxidative stress. In addition, chlorophyll a regulation of nuclear factor (NF) ${\kappa}B$ activation and inducible NO synthase (iNOS) expression were explored as potential mechanisms of NO suppression in a lipopolysaccharide (LPS)-stimulated macrophage cell line. RAW 264.7 murine macrophages were preincubated with various concentrations ($0-10\;{\mu}g/ mL$) of chlorophyll a and stimulated with LPS to induce oxidative stress and inflammatory response. Treatment with chlorophyll a reduced the accumulation of thiobarbituric acid-reactive substances (TBARS), enhancing glutathione level and the activities of antioxidative enzymes including superoxide dismutase, catalase, glutathione peroxidase (GSH-px), and glutathione reductase in LPS-stimulated macrophages compared to LPS-only treated cells. NO production was significantly suppressed in a dose-dependent manner (p<0.05) with an $IC_{50}$ of $12.8\;{\mu}g/mL$. Treatment with chlorophyll a suppressed the levels of iNOS protein and its mRNA expression. The specific DNA binding activities of NFkB on nuclear extracts from chlorophyll a treated cells were significantly suppressed in a dose-dependent manner with an $IC_{50}$ of $10.7\;{\mu}g/mL$. Chlorophyll a ameliorates NO production and iNOS expression through the down-regulation of NFkB activity, which may be mediated by attenuated oxidative stress in RAW 264.7 macrophages.

• Food Science and Biotechnology
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• 제16권4호
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• pp.531-536
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• 2007

The aerial part of Artemisia iwayomogi Kitamura has traditionally been used for inflammation, infectious disease, cancer, pyretic, diuretic, liver protective effect, and choleretic purposes in Korea. We investigated that the essential oil induces apoptosis in KB cell as evidenced by Hoechst-33258 dye staining, flow cytometry (cell cycles), and DNA fragmentation for nuclear condensation and Western blotting for activation of caspases-3, -8, -9, Bax, Bcl-2, cytochrome c, and poly (ADP-ribose) polymerase (PARP) cleavage. In the present study, we found that the essential oil could induce apoptosis in KB cells, as characterized by DNA fragmentation, activation of caspase-3, -8, and -9, and PARP cleavage. The efficacious induction of apoptosis was observed as a dose-dependent. The essential oil-induced apoptotic cell death was accompanied by up-regulation of Bax and down-regulation of Bcl-2. The essential oil also caused the loss of mitochondrial membrane potential and cytochrome c release from mitochondria to cytosol. These findings indicate that mitochondrial pathways might be involved in the essential oil-induced apoptosis and enhance our understanding of the anticancer function of the essential oil in herbal medicine.

• 미생물학회지
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• 제52권1호
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• pp.18-24
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• 2016

본 연구에서는 우수한 아토피 완화능을 가진 유산균을 선별하기 위해 한국인 유아 분변으로부터 23종의 유산균을 분리하였다. 후보 균주들을 배양하여 열처리 된 세포와 상등액 농축물을 각각 얻었다. 우수 균주 선별은 마우스 비장세포를 이용하여 IL-4의 억제 및 IFN-${\gamma}$의 증가 정도를 확인하는 실험을 통해 진행되었다. 선별 실험 결과로 Lactobacillus rhamnosus IDCC 3201 (RH3201)을 OVA로 면역 반응을 유발시킨 BALB/c 마우스에 투여할 유산균으로 선정하였다. RH3201의 균체와 대사물을 경구 투여한 군에서는 유발군에 비해 혈중 IgE의 과다 생성이 억제된 것을 확인하였다. 그러한 알레르기 억제능은 type-1 T helper (Th1) 세포와 type-2 T helper (Th2) 세포의 싸이토카인 간의 균형을 향상시킴으로써 유도되었다. 따라서 RH3201의 균체와 배양물은 면역 조절을 통해 아토피 증상을 완화시킬 수 있음을 확인하였다.