Quercetin-induced Growth Inhibition in Human Bladder Cancer Cells Is Associated with an Increase in Ca^(2+)-activated K^+ Channels

김양미,김운재,차은종 대한약리학회 2011 The Korean Journal of Physiology & Pharmacology Vol.15 No.5

Quercetin (3,3’,4’,5,7-pentahydroxyflavone) is an attractive therapeutic flavonoid for cancer treatment because of its beneficial properties including apoptotic, antioxidant, and antiproliferative effects on cancer cells. However, the exact mechanism of action of quercetin on ion channel modulation is poorly understood in bladder cancer 253J cells. In this study, we demonstrated that large conductance Ca^(2+) activated K^+ (BKCa) or MaxiK channels were functionally expressed in 253J cells, and quercetin increased BKCa current in a concentration dependent and reversible manner using a whole cell patch configuration. The half maximal activation concentration (IC50) of quercetin was 45.5±7.2μM. The quercetin-evoked BKCa current was inhibited by tetraethylammonium (TEA; 5 mM) a non-specific BKCa blocker and iberiotoxin (IBX; 100 nM) a BKCa-specific blocker. Quercetin-induced membrane hyperpolarization was measured by fluorescence-activated cell sorting (FACS) with voltage sensitive dye, bis (1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC4(3); 100 nM). Quercetin-evoked hyperpolarization was prevented by TEA. Quercetin produced an antiproliferative effect (30.3±13.5%) which was recovered to 53.3±10.5% and 72.9±3.7% by TEA and IBX, respectively. Taken together our results indicate that activation of BKCa channels may be considered an important target related to the action of quercetin on human bladder cancer cells.

Anti-Inflammatory Effects of 3-(40-Hydroxyl-30,50-Dimethoxyphenyl)Propionic Acid, an Active Component of Korean Cabbage Kimchi, in Lipopolysaccharide-Stimulated BV2 Microglia

정진우,최일환,김기영,김진우,서홍석,류충호,김운재,박건영,최영현,조국희 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.6

We investigated the protective ability of 3-(40-hydroxyl-30,50-dimethoxyphenyl)propionic acid (HDMPPA), an active principle in Korean cabbage kimchi, against the production of proinflammatory mediators and cytokines, and the mechanisms involved in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. HDMPPA significantly suppressed the production of nitric oxide (NO) and prostaglandin E2, along with the expression of inducible NO synthase and cyclooxygenase-2 in LPS-stimulated BV2 cells, at concentrations with no cytotoxicity. HDMPPA also attenuated the LPS-induced expression and secretion of proinflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β. Furthermore, HDMPPA inhibited LPS-induced nuclear factor-κB (NF-κB) activation, which was associated with the abrogation of IκB-a degradation and phosphorylation, and subsequent decreases in NF-κB p65 levels. Moreover, the phosphorylation of mitogen-activated protein kinases (MAPKs) and Akt, a downstream molecule of phosphatidylinositol-3-kinase (PI3K), in LPS-stimulated BV2 cells was suppressed markedly by HDMPPA. This effect was associated with a significant reduction in the formation of intracellular reactive oxygen species. The findings in this study suggest that HDMPPA may exert anti-inflammatory responses by suppressing LPS-induced expression of proinflammatory mediators and cytokines through blockage of NF-κB, MAPKs, and PI3K/Akt signaling pathways and oxidative stress in microglia.

Docetaxel-Induced Fatal Interstitial Pneumonitis in a Patient with Castration-Resistant Prostate Cancer

민병달,강호원,김원태,김용준,윤석중,이상철,김운재 대한비뇨의학회 2012 Investigative and Clinical Urology Vol.53 No.5

A 69-year-old man with castration-resistant prostate cancer (CRPC) received docetaxel and a corticosteroid. After the third cycle of docetaxel administration, he presented with dyspnea, cough, sputum, and fever of 39.2oC. The chest X-ray and chest computed tomography (CT) revealed a diffuse reticulonodular shadow in both lungs, which suggested interstitial pneumonitis. Initially, we used empiric broad-spectrum antibiotics and high-dose corticosteroids. However, his condition progressively became worse and he was transferred to the intensive care unit, intubated, and placed on mechanical ventilation. He died 4 days after hospital admission. Here we report this case of fatal interstitial pneumonitis after treatment with docetaxel for CRPC. We briefly consider docetaxel-induced pneumonitis to make physicians aware of the possibility of pulmonary toxicity so that appropriate treatment can be begun as soon as possible.

Peanut Sprout Extracts Cultivated with Fermented Sawdust Medium Inhibits Benign Prostatic Hyperplasia In Vitro and In Vivo

송준휘,황병두,정현주,문보경,김진욱,고기성,김배환,김원룡,김운재,명순철,문성권 대한남성과학회 2020 The World Journal of Men's Health Vol.38 No.3

Purpose: In this study, we tested whether the resveratrol-enriched peanut sprout extracts cultivated with fermented sawdust medium (PSEFS) could suppress benign prostatic hyperplasia (BPH) in vitro and in vivo. Materials and Methods: The mode of action of PSEFS was estimated by employing high-performance liquid chromatography analysis, MTT assay, cell counting, cell cycle analysis, immunoblots, and immunoprecipitation and electrophoretic mobility shift assay. In vivo efficacy of PSEFS was analyzed in BPH animal model via immunostaining and enzyme-linked immunosorbent assay. Results: We selected the Yesan peanut sprout variety, which contains the highest level of resveratrol. The resveratrol levels in PSEFS were higher than those obtained with hydroponic technology. PSEFS treatment induced cell cycle arrest at the G1- phase by downregulating CDK4 and cyclin D1 via p21WAF1 induction in the RWPE-1 and WPMY prostate cells, thereby decreasing their proliferation. Treatment with PSEFS decreased ERK1/2 phosphorylation and increased JNK phosphorylation. The levels of DNA-bound transcription factors associated with proliferation (nuclear factor-κB, Sp-1, and AP-1) decreased upon PSEFS treatment in both prostate cells. Additionally, the levels of the molecular markers of BPH development (5α-reductase, androgen receptor, fibroblast growth factor, Bcl-2, and Bax) also changed by the addition of PSEFS. Finally, in a testosterone propionate-induced BPH model in rats, PSEFS administration attenuated the size, weight, and thickness of prostate tissues with no signs of death. Conclusions: These results showed that PSEFS inhibited BPH both in vitro and in vivo and might be useful in the development of a potential BPH therapy.

연소촉매 FeOOH를 포함하는 고체추진제 특성 연구: FeOOH의 소성온도 영향

전수아(Su-A Jeon),박성준(Sung-Jun Park),김운재(Woon-Jae Kim),박정호(Jung-ho Park) 한국추진공학회 2020 한국추진공학회지 Vol.24 No.6

황색산화철 자연노화에 따른 고체 추진제 특성 연구

박성준(Sungjun Park),최성한(Sunghan Choi),전수아(Sua Jeon),김가희(Kahee Kim),김경민(Kyungmin Kim),김운재(Woonjae Kim),박정호(Jungho Park) 한국추진공학회 2020 한국추진공학회 학술대회논문집 Vol.2020 No.11

혼합형 고체 추진제에 황색산화철은 연소촉매로 사용되며 고온, 고압에서 압력지수 값이 낮은 특성이 있다. 황색산화철은 수화물 형태이며 열과 압력 등에 의해 Fe₂O₃와 H₂O로 분해된다. 이렇게 분해 되면서 발생 한 수분에 의해 추진기관의 수명에 악영향을 끼칠 수 있다. 본 연구에서는 황색산화철의 자연 노화에 따른 결정상 변화, 휘발성 및 열분해 특성 그리고 밀도를 확인하였다. 또한 자연 노화된 황색산화철을 고체추진제에 적용하여 추진제의 초기점도, 연소속도와 인장강도 결과를 통해 연소촉매로써의 성능을 나타낼 수 있는지 확인하였다. Yellow iron oxide is a hydrate and decomposes into Fe₂O₃ and H₂O under heat and pressure. Moisture generated during decomposition can adversely affect the life of the propulsion rocket. In this study, the crystal phase change, volatility and pyrolysis characteristics, and the density of yellow iron oxide were confirmed according to natural aging. In addition, naturally aged yellow iron oxide was applied to the solid propellant, and the initial viscosity, combustion rate, and tensile strength results of the propellant were checked to see if it can exhibit the performance as a burning rate catalyst.

Methylation Signature for Prediction of Progression Free Survival in Surgically Treated Clear Cell Renal Cell Carcinoma

강호원,박홍용,서성필,변영준,Xuan-Mei Piao,김성민,김원태,윤석중,장우영,손호선,류근호,이상철,김운재,김용준 대한의학회 2019 Journal of Korean medical science Vol.34 No.19

Background: Little is known about epigenetic silencing of genes by promoter hypermethylation in renal cell carcinoma (RCC). The aim of this study was to identify prognostic methylation markers in surgically treated clear cell RCC (ccRCC). Methods: Methylation patterns were assayed using the Infinium HumanMethylation450 BeadChip array on pairs of ccRCC and normal tissue from 12 patients. Using quantitative PSQ analysis, tumor-specific hypermethylated genes were validated in 25 independent cohorts and their clinical relevance was also verified in 152 independent cohorts. Results: Using genome-wide methylation array, Zinc finger protein 278 (ZNF278), Family with sequence similarity 155 member A (FAM155A) and Dipeptidyl peptidase 6 (DPP6) were selected for tumor-specific hypermethylated genes in primary ccRCC. The promoter methylation of these genes occurred more frequently in ccRCC than normal kidney in independent validation cohort. The hypermethylation of three genes were associated with advanced tumor stage and high grade tumor in ccRCC. During median follow-up of 39.2 (interquartile range, 15.4–79.1) months, 22 (14.5%) patients experienced distant metastasis. Multivariate analysis identified the methylation status of these three genes, either alone, or in a combined risk score as an independent predictor of distant metastasis. Conclusion: The promoter methylation of ZNF278, FAM155A and DPP6 genes are associated with aggressive tumor phenotype and early development of distant metastasis in patients with surgically treated ccRCC. These potential methylation markers, either alone, or in combination, could provide novel targets for development of individualized therapeutic and prevention regimens