• Journal of Acupuncture Research
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• v.24 no.2
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• pp.15-29
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• 2007

목적 : 후박(厚朴)(Magnolia Obovata)에서 추출한 낮은 농도의 Obovatol 약침액의 RAW264.7 세포에서 LPS로 유발된 염증，$TNF-{\alpha}$로 유발된 human Prostate carcinoma PC-3 및 LNCap 세포의 세포증식에 대한 영향과 그 기전을 살펴보고자 하였다. 방법 : RAW264.7 세포에서 LPS로 염증을 유발하고 낮은 농도의 Obovatol 약침액을 처리한 후 cell viability, NO 생성량，iNOS와 COX-2의 발현, $NF-{\kappa}B$활성，전사능력을 관찰하기 위해 MTT assay, NO determination assay, western blot analysis, EMSA, luciferase activity assay를 시행하였고，LNCap, PC-3 세포에 $TNF-{\alpha}$로 증식을 유도하고 낮은 농도의 Obovatol 약침액을 처리한 후 cell growth, apoptosis 및 apoptosis와 연관된 $NF-{\kappa}B$의 활성 변화를 관찰하기 위해 WST-1, Cell morphogy test, DAPI staining and TUNEL assay, EMSA, luciferase activity assay를 시행하였다. 결과 : 1. RAW264.7 세포에서 낮은 농도의 Obovatol 약침액 처리는 $NF-{\kappa}B$의 활성 및 전사능력을 낮추고 iNOS와 COX-2의 발현과 NO 생성을 감소시켜 LPS로 유발된 염증을 억제하였다. 2. LNCap, PC-3 세포에서 낮은 농도의 Obovatol 약침액 처리는 $NF-{\kappa}B$의 활성을 낮추어 세포자별사를 촉진함으로써 $TNF-{\alpha}$로 유발된 암세포의 성장을 억제하였다. 결론 : 이상의 결과는 낮은 농도의 Obovatol 약침액이 항염 및 인간 전립선암세포주인 PC-3, LNCap에 대한 증식억제 효과가 있음을 입증한 것이며，향후 이를 바탕으로한 생체 연구에서의 긍정적인 결과는 Obovatol 약침액이 만성염증성 질환 및 전립선암의 예방과 치료에 대한 효과적인 치료제 개발에 초석이 될 것으로 기대된다.

• Journal of Life Science
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• v.24 no.1
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• pp.92-97
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• 2014

Cordycepin, an active component originally isolated from the traditional medicine Cordyceps militaris, is a derivative of the nucleoside adenosine, which has been shown to possess a number of pharmacological properties, including antioxidant and anti-inflammatory activities, immunological stimulation, and antitumor effects. This study was conducted on cultured human prostate carcinoma LNCap cells to elucidate the possible mechanisms by which cordycepin exerts its anticancer activity, which, until now, has remained poorly understood. Cordycepin treatment of LNCap cells resulted in dose-dependent inhibition of cell growth and the induction of apoptotic cell death as detected by an MTT assay, cleavage of poly ADP-ribose polymerase, and annexin V-FITC staining. Flow cytometric analysis revealed that cordycepin resulted in G2/M arrest in cell cycle progression and downregulation of cyclin B1 and cyclin A expression in a concentration-dependent manner. Moreover, the incubation of cells with cordycepin caused a striking induction in the expression of the cyclin-dependent kinase (CDK) inhibitor p21Waf1/Cip1 without affecting the expression of the tumor suppressor p53. It also resulted in a significant increase in the binding of CDK2 and CDC2 to p21. These findings suggest that cordycepin-induced G2/M arrest and apoptosis in human prostate carcinoma cells is mediated through p53-independent upregulation of the CDK inhibitor p21.

• Journal of Life Science
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• v.24 no.6
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• pp.700-706
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• 2014

Doxorubicin (trade name adriamycin), an anthracycline antibiotic, is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. It is closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA. Its most serious adverse effect is life-threatening heart damage. Its anti-metastatic mechanisms in human prostate carcinomas are not fully understood. In this study, we used LNCap human prostate carcinoma cells to investigate the inhibitory effects of doxorubicin on cell motility and invasion, two critical cellular processes that are often deregulated during metastasis. Doxorubicin treatment inhibited cell migration and invasiveness of LNCap cells without showing any toxicity. Doxorubicin treatment also suppressed the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were associated with up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in LNCap cells. Doxorubicin treatment also attenuated the expression levels of claudin family members (claudin-1, -2,-3 and -4), major components of tightening of tight junctions (TJs) and increased the tightening of TJs, as demonstrated by an increase in transepithelial electrical resistance. The present findings demonstrate that doxorubicin reduces the migration and invasion of prostate carcinomas LNCap cells by modulating the activity of TJs and MMPs.

• Bulletin of the Korean Chemical Society
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• v.33 no.1
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• pp.111-114
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• 2012

Androgen receptor (AR) is ligand-inducible nuclear hormone receptor which has been focused on key molecular target in growth and progression of prostate cancer. We synthesized a series of 4-aryl 2-substituted aniline-thiazole analogs and evaluated their anti-cancer activity in AR-dependent human prostate cancer LNCap cells. Among them, the compound 6 inhibited the tumor growth in LNCap-inoculated xenograft model.

• Journal of Life Science
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• v.29 no.10
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• pp.1159-1163
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• 2019

Although there is a growing interest in male menopause, a phenomenon associated with male hormone depletion, current kits using antibodies to quantify male hormones are expensive. In this study, we constructed an in vitro system for verifying the activity or concentration of male steroid hormones using a transcriptional activity test. A reporter plasmid, pGL2-Neo-ARE-AdE1BTATA, which reacts to testosterone, was constructed. In this plasmid, the ARE-AdE1bTATA sequences can be bounded by the testosterone - androgen receptor complex to express luciferase as a reporter. Then, a stable transfection was performed on the human prostate cancer cell line, LNcap-LN3. The constructed LNcap-LN3/pGL2-Neo-ARE-AdE1BTATA testosterone compound detection (TCD) system showed quantitatively proportional luciferase activities to concentrations of $10^{-13}$ to $10^{-8}M$ of standard testosterone. The established in vitro TCD system will contribute to the development of materials for health/functional foods and drugs as it will be possible to search en masse for testosterone-like or testosterone-inhibiting substances derived from natural materials.

• Natural Product Sciences
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• v.27 no.4
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• pp.274-279
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• 2021

The therapeutic effects of the leaves of Couroupita guianensis, a large tropical tree in the family of Lecythidaceae improving testosterone-induced Benign Prostatic Hyperplasia (BPH) were tested in vitro and in vivo. In BPH rats induced by castration and testosterone treatment, the prostate index was improved in groups administered with the extracts of C. guianensis extracted with 50%-, 100%-ethanol or boiling water, which was comparable with positive control, finasteride. The extract C. guianensis leaves showed significant inhibition on the expressions of type 2 5-alpha reductase (5αR) in RWPE-1 human prostatic epithelial cells, and effectively attenuated the expressions of androgen receptor, type 2 5αR and proliferating cell nuclear antigen in LNCap human prostatic adenocarcinoma cells. The leaves of C. guianensis that exerted evident suppression on BPH-related biomarkers in vitro and improvement of prostate index in vivo has a potential therapeutic use for the treatment of BPH.

• Bulletin of the Korean Chemical Society
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• v.35 no.7
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• pp.2038-2042
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• 2014

4-(tert-Octyl)phenol derivatives bearing the D-mannitol substructure (6a, 6b, 7) were prepared from $\small{D}$-mannitol and evaluated their anticancer activity against human lung (A549) and prostate (Lncap, Du145, PC3) cancer cell lines. Among derivatives tested, the bis(tert-octyl)phenoxy compound 7 exhibited strongest proliferation inhibitory activities against human cancer cell lines tested, especially high sensitivity to human Du145 prostate cancer cells ($IC_{50}=7.3{\mu}M$).

• Environmental Mutagens and Carcinogens
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• v.21 no.1
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• pp.34-43
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• 2001

Di-2-ethylhexyl phthalate (DEHP) is the most commonly used phthalate ester in polyvinyl chloride formulations including food packing and storage of human blood. DEHP is a well known as non-genotoxic carcinogen and endocrine disrupting chemical (EDC). DEHP have shown all negative results in ICH-guildeline recommended standard genotoxicity test battery. In this study, to assess the clastogenic and DNA damaging effect in human-derived tissue specific cells, DEHP was treated in human derived MCE-7 cells, HepG2 cells, LNCap cells, BeWo cells, MCE-10A cells, and female peripheral blood cells using micronucleus assay and in human breast carcinoma MCF-7 cells up to $1.28$\times$10^{-2}$ M using Comet assay. The in vitro micronucleus assay is a mutagenicity test system for the detection of chemicals which induce the formation of small membrane bound DNA fragment i.e. micronuclei in the cytoplasm of interphase cells, originated from clastogenic and/or aneugenic mechanism. The single cell gel electrophoresis assay (Comet assay) is used to detect DNA strand-breaks and alkaline labile site. In our results, DEHP increased significantly and/or dose-depentently and time-dependently micronucleus frequency at the 6 and 24 hr without metabolic activation system only in MCE-7 cells. DEHP treated with 2 hrs in MCF-7 cells using Comet assay induced DNA damage dose-depentantly.

• Food Science and Biotechnology
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• v.18 no.1
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• pp.108-112
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• 2009

Antioxidant and anticancer effects of methanolic extracts from the flesh (WFME) and peel (WPME) of white onion, the flesh (YFME) and peel (YPME) of yellow onion, the flesh (RFME) and peel (RPME) of red onion were studied. The content of total phenolics in WFME, WPME, YPME, YFME, RPME, and RFME were $0.260{\pm}0.01$, $4.480{\pm}0.23$, $0.319{\pm}0.02$, $719.12{\pm}37.36$, $0.248{\pm}0.01$, and $806.21{\pm}26.38\;mg/g$, respectively. The quercetin content of WFME, WPME, YFME, YPME, RFME, and RPME were $12.56{\pm}0.19$, $3.57{\pm}0.14$, $15.24{\pm}0.65$, $755.29{\pm}22.24$, $5.70{\pm}0.23$, and $774.03{\pm}29.48\;mg$/100 g, respectively. Like total phenolics, the highest 2,2'-diphenyl-1-picrylhydrazyl (DPPH) scavenging activities were found in RPME. However, inhibitory effects on lipid oxidation of RPME were similar to those of WPME and YPME. In addition, inhibitory effect of WPME, YPME, and RPME for human breast cancer cell (MCF-7) growth were 78.43, 81.90, and 96.52% while those on human prostate cancer cell (LNcap) were 71.58, 77.93, and 98.47% at $100{\mu}g/mL$, respectively. Total phenolics, quercetin content, antioxidant, and anticancer activities exhibited significant variation among the 3 onion varieties in this experiment. Therefore, it is assumed that antioxidant and anticancer activities were affected by the total phenolics and quercetin level of onion.

• Molecules and Cells
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• v.37 no.2
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• pp.178-186
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• 2014

Differential transcription of the clusterin (CLU) gene yields two CLU isoforms, a nuclear form (nCLU) and a secretory form (sCLU), which play crucial roles in prostate tumorigenesis. Pro-apoptotic nCLU and anti-apoptotic sCLU have opposite effects and are differentially expressed in normal and cancer cells; however, their regulatory mechanisms at the transcriptional level are not yet known. Here, we examined the transcriptional regulation of nCLU in response to hypoxia. We identified three putative hypoxia response elements (HREs) in the human CLU promoter between positions -806 and +51 bp. Using a luciferase reporter, electrophoretic gel mobility shift, and chromatin immunoprecipitation assays, we further showed that hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) bound directly to these sites and activated transcription. Exposure to the hypoxia-mimetic compound $CoCl_2$, incubation under 1% $O_2$ conditions, or overexpression of HIF-$1{\alpha}$ enhanced nCLU expression and induced apoptosis in human prostate cancer PC3M cells. However, LNCaP prostate cancer cells were resistant to hypoxia-induced cell death. Methylation-specific PCR analysis revealed that the CLU promoter in PC3M cells was not methylated; in contrast, the CLU promoter in LNCap cells was methylated. Co-treatment of LNCaP cells with $CoCl_2$ and a demethylating agent promoted apoptotic cell death through the induction of nCLU. We conclude that nCLU expression is regulated by direct binding of HIF-$1{\alpha}$ to HRE sites and is epigenetically controlled by methylation of its promoter region.