• Journal of Acupuncture Research
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• 제33권1호
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• pp.47-56
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• 2016

Objectives : This study examined the effects of Bee venom on apoptosis in NCI-H157 human lung cancer cells and for promoting the apoptosis effects of Natural killer cell. Methods : Bee venom and Natural killer-92 cells were cultured either separately from or together with NCI-H157 cells for 24 hours. To figure out whether Bee venom enhances the cytotoxic effect of Natural Killer-92 cells, a cell viability assay was conducted. To observe the changes in Death receptors, apoptotic regulatory proteins and Nuclear $Factor-{\kappa}B$, western blot analysis was conducted. To observe the effect of Bee venom through an extrinsic mechanism, a transfection assay was conducted. Results : 1. Natural killer-92 cells and Bee venom significantly inhibited the growth of NCI-H157 cells and co-culture had more inhibitory effect than the separate culture. 2. Expressions of Fas, DR3, DR6, Bax, caspase-3, caspase-8, cleaved caspase-3, cleaved caspase-8 were increased, and expressions of Bcl-2 and cIAP were decreased. More efficacy was observed in co-culture than in separate culture. 3. Nuclear $Factor-{\kappa}B$ activation was clearly decreased. And co-culture showed much less activation than separate culture. 4. As a result of treatment for DR-siRNA, the reduced cell viability of NCI-H157 cells and the activity of Nuclear $Factor-{\kappa}B$ were increased. With this, it can be seen that Bee venom and Natural killer-92 cells have an effect on the cancer cells through the extrinsic mechanism. Conclusion : Bee venom is effective in inhibiting the growth of human lung cancer cells. Furthermore Bee venom effectively enhances the functions of Natural killer cells.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5855-5860
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• 2013

Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking or reversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer related death. One such promising chemopreventive agent which has attracted considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. The present study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent, gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the results by nuclear morphological examination. Further we analyzed the modulation of expression of Bcl-2 and COX-2 on treatment of these cells with SFN by RT-PCR. SFN showed cytotoxic effects on MCF-7 cells in a dose- and time-dependent manner via an apoptotic mode of cell death. In addition, a combinational treatment of SFN and gemcitabine on MCF-7 cells resulted in growth inhibition in a synergistic manner with a combination index (CI)<1. Notably, SFN was found to significantly downregulate the expression of Bcl-2, an anti-apoptotic gene, and COX-2, a gene involved in inflammation, in a time-dependent manner. These results indicate that SFN induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 and COX-2 respectively. The combination of SFN and gemcitabine may potentiate the efficacy of gemcitabine and minimize the toxicity to normal cells. Taken together, SFN may be a potent anti-cancer agent for breast cancer treatment.

• BMB Reports
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• 제31권1호
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• pp.83-88
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• 1998

Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4 (IL-4) and CD40 ligation in B cell activation, we have examined the effect of CE40 cross-linking on the IL-4 receptor expression in human B cells using anti-CE40 antibody. We observed that IL-4 and anti-CD40 both induce IL-4 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in a significant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4 action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

• 한국발생생물학회지:발생과생식
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• 제22권2호
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• pp.133-142
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• 2018

Patients with type II diabetes mellitus are more susceptible to colorectal cancer (CRC) incidence than non-diabetics. The anti-diabetic drug metformin is most commonly prescribed for the treatment of this disease and has recently shown antitumor effect in preclinical studies. The aberrant mutational activation in the components of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathway is very frequently observed in CRC. We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Therefore, we hypothesized that simultaneous inhibition of two pathways by combining metformin with BEZ235 could be more effective in the suppression of proliferation than single agent treatment in HCT15 CRC cells. Here, we investigated the combinatory effect of metformin and BEZ235 on the cell survival in HCT15 CRC cells. Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. This combination treatment synergistically reduced cell viability. The combination index (CI) values ranged from 0.44 to 0.88, indicating synergism for the combination. These results offer a preclinical rationale for the potential therapeutic option for the treatment of CRC.

• 자원환경지질
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• 제43권2호
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• pp.101-107
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• 2010

폐광지역 비소오염 토양에 이용될 식물상복원공법으로서 논에서 쉽게 발견되는 피의 적용가능성을 알아보고자 하였다. 식물을 이용한 토양 정화 공법이 가지는 장기간의 처리시간이 소요된다는 단점을 해결하고자 PSM(phosphate-solubilizing microbes)과 EDTA(ethylenediaminetetraacetic acid)를 처리하여 그 상승효과를 관찰하였다. PSM을 처리한 시험구에서는 식물의 바이오매스가 증가하여 비교 시험구에 비하여 비소재거 효율이 약 16% 정도 증가하였다. EDTA 처리구에서는 토양 내 중금속의 이동성야 증가하여 BF(bioaccumulation factor) 는 증가하였으나, EDTA가 식풀의 성장을 저해해 오히려 제거 효율이 20% 정도 감소하는 결과를 가져왔다. 따라서 식물성복원공법에 PSM 및 EDTA의 처리는 식물의 비소 흡수를 어느 정도 증대시킬 수는 있으나, 특히 EDTA를 처리할 경우에는 처리 시기 및 처리량의 선택에 있어서 식물의 성장을 저해하지 않도록 해야 하며, 지속적인 모니터링이 요구된다는 결과를 얻었다.

• 동의생리병리학회지
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• 제22권5호
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• pp.1262-1269
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• 2008

Low intensity pulsed ultrasound(LIPUS) is known to accelerate bone regeneration, but the precise cellular signaling mechanism is still unclear. The purpose if this study was to determine the effect of LIPUS on the signaling mechanism of rat chondrocyte. In the explant culture condition, there was inhibition effect of 1 $W/cm^2$ intensity LIPUS on chondrocytes proliferation but chondrocytes proliferation was increased at 0.25 $W/cm^2$ intensity. In addition, western blot analysis of MAPKs showed that LIPUS increased ERK1/2 activity from the 10 min treatment of LIPUS. Hydrogen peroxide($H_2O_2$), resulted in a time- and dose-dependent cell proliferation, which was largely attributed to apoptosis. $H_2O_2$ treatment caused marked sustained nucleus condensation in Hoechst stain. LIPUS and $H_2O_2$ activates phosphorylation of p-ERK1/2 and PD 98059($10^{-5}M$) blocked the effect of LIPUS and $H_2O_2$. Moreover, the synergistic phosphorylation of p44/42 MAPK by $H_2O_2$, LIPUS was selectively inhibited by PD 98059, ERK1/2 inhibitor. In order to determine whether the increase in cell proliferation caused by $H_2O_2$ and LIPUS could be explained by changes in the level of the prostaglandin $E_2$. Our study demonstrated that LIPUS stimulate the cell proliferation via activated phosphorylation of ERK1/2 in condrocyte. LIPUS has anabolic effects on rat cartilage in explant cultures, indicating a potential important method for the treatment of osteoarthritic cartilarge.

• 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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• 제24권1호
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• pp.85-93
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• 2016

We already reported that genetically engineered resveratrol-enriched rice (RR) showed to down-regulate skin melanogenesis. To be developed to increase the bioactivity of RR using calli from plants, RR was adopted for mass production using plant tissue culture technologies. In addition, high-pressure homogenization (HPH) was used to increase the biocompatibility and penetration of the calli from RR into the skin. We aimed to develop anti-melanogenic agents incorporating calli of RR (cRR) and nanoparticles by high-pressure homogenization, examining the synergistic effects on the inhibition of UVB-induced hyperpigmentation. Depigmentation was observed following topical application of micro-cRR, nano-calli of normal rice (cNR), and nano-cRR to ultraviolet B (UVB)-stimulated hyperpigmented guinea pig dorsal skin. Colorimetric analysis, tyrosinase immunostaining, and Fontana-Masson staining for UVB-promoted melanin were performed. Nano-cRR inhibited changes in the melanin color index caused by UVB-promoted hyperpigmentation, and demonstrated stronger anti-melanogenic potential than micro-cRR. In epidermal skin, nano-cRR repressed UVB-promoted melanin granules, thereby suppressing hyperpigmentation. The UVB-enhanced, highly expressed tyrosinase in the basal layer of the epidermis was inhibited by nano-cRR more prominently than by micro-cRR and nano-cNR. The anti-melanogenic potency of nano-cRR also depended on pH and particle size. Nano-cRR shows promising potential to regulate skin pigmentation following UVB exposure.

• Journal of Ginseng Research
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• 제22권2호
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• pp.140-146
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• 1998

It was founded that an X-compound is contained in extracts from the root of old red ginseng (6RG) compared with that from the root of 4-year old red ginseng(4RG). Both water extract and petroleum ether extract (PEII) from 6RG or 4RG inhibited the release of [$^{3}H$]-serotonin induced by platelet activating factor (PAF; 40 ng/ml). Water extract and PEll from 6RG Inhibited potently PAF-induced [$^{3}H$]-serotonin release compared with those from 4RG. X-compound out of both water extract and PEll from 6RG inhibited the release of [$^{3}H$]-serotonin inducted by collagen (100 $\mu\textrm{g}$/ml) or thrombin(20 U/ml). X-compound had a synergistic effect with water extract from 4RG on collagen-and thrombin-induced [3H] -serotonin release out of human platelets. The concentration(IC50) of X-compound that require to inhibit 50% of [$^{3}H$]-serotonin-release was 3.25 $\mu\textrm{g}$/ml, and it is inferred that maximum concentration of X-compound that inhibits the release of [$^{3}H$]-serotonin is 10 $\mu\textrm{g}$/ml. Because thrombosis is resulted mainly from the irreversible aggregations which are intimately related with the serotonin release and migraine is also caused when serotonin is released, it is inferred that water extract, PEII and X-compound from 6RG have antithrombosis and antimigrainous functions by inhibiting the release of serotonin from human platelets.

• 한국식품저장유통학회지
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• 제8권4호
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• pp.385-392
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• 2001

다양한 침지 저장액에 의한 깐밤의 갈변억제에 따른 저장 효과를 비교하였다. 총 폴리페놀의 함량은 저장초기에 13.36 mg%로 매우 낮게 나타났으나, 무처리구는 저장 17일까지 59.12 mg%로 증가 후 다시 감소하였다. 전해산화수 처리구는 저장 8일에 61.02 mg%로 갑작스런 증가를 보인 후 감소하였고, 그 외의 처리구에서는 저장 초기에 미세한 변화를 보이다가 저장 11일에 갑작 스럽게 증가하는 경량을 나타내었다. Polyphenol oxidase 활성의 변화는 기질의 증가시기보다 조금 앞서 증가되기 시작하였으며, 무처리구가 저장 11일에 1,152 units로 가장 높은 활성을 나타내었다. 그리고 명반수 처리구가 저장 8일에 1,117 units로 다른 처리구에 비하여 높은 활성을 나타내었다. 4주간 저장하였을 때에는 유자와 레몬과즙 첨가 전해산화수 처리구가 각각 143.3 units와 180.22 units을 나타내어 타 처리구에 비하여 갈변이 억제되는 것으로 나타났다. 색도 및 관능검사를 통하여 저장기간을 예측하며 본 결과, 무처리구의 경우는 14일, 명반수, 전해산화수 및 NaCl을 첨가한 전해산화수의 경우는 21일, 유자와 레몬을 첨가한 전해산화수 처리구는 28일까지도 저장이 가능한 것으로 나타났다.