• Molecules and Cells
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• 제37권2호
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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.

• 한국축산식품학회지
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• 제35권4호
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• pp.507-514
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• 2015

Deer velvet antler (DVA) is one of the most popular medicines in China. Numerous studies have demonstrated that velvet antler possess biological effects. However, data regarding its anti-migration activity on prostate cancer is scarce. In this study, we investigated the inhibitory effect of top DVA (T-DVA) on the expression of prostate-specific antigen (PSA) and migration-related genes in the human prostate cancer cell, LNCaP. The T-DVA down-regulated the expression of PSA. In addition, the Radius^TM assay revealed that T-DVA inhibited the migration behavior of prostate cancer cells. Furthermore, the expression of matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) was also decreased with T-DVA. On the contrary, T-DVA increased the tissue inhibition of metallo-proteinase (TIMP)-1 and (TIMP)-2. Taken together, our findings indicate that the T-DVA possesses anti-migration activity on prostate cancer cells. This is the first study of DVA to report the anti-migration activity on prostate cancer.

• 한국식품영양과학회지
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• 제43권2호
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• pp.318-322
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• 2014

본 연구에서는 울금(Curcuma longa L.)의 다양한 추출물을 대상으로 5-alpha reductase의 활성 저해 정도를 측정하였다. 5-Alpha reductase는 T에서 활성형 남성호르몬인 DHT로 전환을 담당하며, 전립선비대에서는 혈액에서 DHT 농도가 높다. Rat의 전립선조직 균질액과 5-alpha reductase를 과발현시킨 LNCaP 세포 균질액을 대상으로 측정한 결과, $100{\mu}g/mL$의 농도에서 울금의 열수추출물(CL-HW)과 20% 에탄올추출물(CL-E20)이 5-alpha reductase 활성을 효과적으로 저해하였다. 특히 CL-HW는 $100{\mu}g/mL$의 농도에서 80% 이상의 유의적 억제효과를 보였으며, CL-E20은 $50{\mu}g/mL$의 농도부터 80% 이상의 감소효과를 보였다. 이 같은 결과에서 CL-HW 및 CL-E20은 5-alpha reductase의 억제활성이 있으며, 이는 전립선비대 치료소재로 개발될 수 있는 가능성이 있음을 제안한다.

• Biomaterials and Biomechanics in Bioengineering
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• 제3권3호
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• pp.129-140
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• 2016

This article reports the development of biodegradable photoluminescent polymer (BPLP)-based nanoparticles (NPs) incorporating either magnetic nanoparticles (BPLP-MNPs) or gadopentate dimeglumine (BPLP-Gd NPs), for cancer diagnosis and treatment. The aim of the study is to compare these nanoparticles in terms of their surface properties, fluorescence intensities, MR imaging capabilities, and in vitro characteristics to choose the most promising dual-imaging nanoprobe. Results indicate that BPLP-MNPs and BPLP-Gd NPs had a size of $195{\pm}43nm$ and $161{\pm}55nm$, respectively and showed good stability in DI water and 10% serum for 5 days. BPLP-Gd NPs showed similar fluorescence as the original BPLP materials under UV light, whereas BPLP-MNPs showed comparatively less fluorescence. VSM and MRI confirmed that the NPs retained their magnetic properties following encapsulation within BPLP. Further, in vitro studies using HPV-7 immortalized prostate epithelial cells and human dermal fibroblasts (HDFs) showed > 70% cell viability up to $100{\mu}g/ml$ NP concentration. Dose-dependent uptake of both types of NPs by PC3 and LNCaP prostate cancer cells was also observed. Thus, our results indicate that BPLP-Gd NPs would be more appropriate for use as a dual-imaging probe as the contrast agent does not mask the fluorescence of the polymer. Future studies would involve in vivo imaging following administration of BPLP-Gd NPs for biomedical applications including cancer detection.

• Natural Product Sciences
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• 제25권3호
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• pp.200-207
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• 2019

Albizzia julibrissin (AJ) is an herbal medicine that shows low toxicity, promotes promoting blood circulation and mitigates the inflammation and has mild side effects. Benign prostate hyperplasia (BPH) is one of the most common diseases that occurs in older males and often results in lower urinary tract symptoms. This study was conducted to evaluate the protective effect of AJ against BPH using LNCaP cells and Sprague Dawley rats treated with testosterone. Treatment with AJ extract reduced the expression of androgen receptor (AR) and prostate-specific antigen (PSA) in vitro. In vivo, rats were divided into 6 groups: 1 (Normal Control); 2 (Testosterone propionate (TP) alone); 3 (TP + finasteride); 4 (TP + AJ 10 mg/kg); 5 (TP + AJ 50 mg/kg); 6 (TP + AJ 300 mg/kg). The groups treated with AJ showed reduced the relative prostate weights and BPH-related proteins were altered, with decreased AR, PSA and proliferating cell nuclear antigen (PCNA) observed by western blot. Histopathological analysis revealed the therapeutic effect of AJ, with a decreased thickness of epithelial cells and reduced level of PCNA and $5{\alpha}$-reductase type 2. These results suggest that AJ extract could ameliorate testosterone-induced benign prostatic hyperplasia.

• 한국작물학회지
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• 제56권1호
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• pp.1-7
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• 2011

기능성을 갖는 다양한 물질을 탐색하여 자원의 효율적인 이용, 즉 새로운 기능성을 함유한 생리활성 물질의 발굴 및 국민보건 증진을 목적으로 가시오갈피의 열매 추출물을 대상으로 항산화 활성, 활성산소 소거능, 항고혈압 활성 및 항암활성을 검증하여 가시오갈피 열매의 활용성 증진 및 신규 기능성 자원화의 기초 자료를 제공하고자한 본 연구의 결과를 요약하면 다음과 같다. l. 가시오갈피 열애 추출물의 항산화 활성을 검정하기 위해 Feton's reagent를 사용한 lipid peroxidation system을 사용하여 측정한 결과 추출물의 농도가 $10{\mu}g/mL$ 수준에서부터 뚜렷한 항산화 활성을 나타내였으며, 모든 농도에서 활성평가의 대조구인 ${\alpha}$-tocopherol보다 높은 항산화 활성을 나타내었다. 반면 자유 라디칼 소거 활성에서는 $11.24{\mu}g/mL$의 항산화 활성 ($IC_{50}$)을 나타내어 대조시약인 ${\alpha}$-tocopherol이나 BHT와 유사한 소거 활성을 나타내었다. 2. 가시오갈피 열매 추출물의 xanthine oxidase 활성 억제 효과를 검토한 결과 xanthine oxidase 활성을 50% 저해하는 데 필요한 농도는 약 $36.9{\mu}g/mL$로 대조 활성물질인(+)-catechin에는 미치지는 못하나 상당히 높은 xanthine oxidasc 억제 활성을 나타내는 것으로 조사되었다. 3. 가시오갈피 열매 추출물을 대상으로 인체 암세포주에 대한 세포생육 억제효과를 SRB법으로 검정한 결과 폐암 세포주인 A549세포 및 결장암 세포주인 HCT-15에서는 가시오갈피 열매 추출물이 활성을 나타내지 않는 반면, 전립선암 세포주인 LNCaP와 백혈병 세포주인 MOLT-4F에서는 암세포의 생육을 50% 억제하는 농도가 $5{\mu}g/mL$으로 우수한 세포독성 효과를 나타내었다. 4. 이상의 결과를 종합해 볼 때 높은 항산화 활성을 나타내는 가시오갈피 열매 추출물은 광범위한 항산화 기작 및 항암 활성을 나타냄으로 신규 기능성 자원으로서 활용도가 매우 넓을 것으로 판단된다.

• Journal of Microbiology and Biotechnology
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• 제28권6호
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• pp.1007-1021
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• 2018

Cancer represents one of the most significant threats to human health on a global scale. Hence, the development of effective cancer prevention strategies, as well as the discovery of novel therapeutic agents against cancer, is urgently required. In light of this challenge, this research aimed to evaluate the effects of several potent bioactive peptides and proteins contained in crocodile white blood cell extract (cWBC) against LU-1, LNCaP, PC-3, MCF-7, and CaCo-2 cancer cell lines. The results demonstrate that 25, 50, 100, and $200{\mu}g/ml$ cWBC exhibits a strong cytotoxic effect against all investigated cell lines ($IC_{50}$ $70.34-101.0{\mu}g/ml$), while showing no signs of cytotoxicity towards noncancerous Vero and HaCaT cells. Specifically, cWBC treatment caused a significant reduction in the cancerous cells' colony forming ability. A remarkable suppression of cancerous cell migration was observed after treatment with cWBC, indicating potent antimetastatic properties. The mechanism involved in the cancer cell cytotoxicity of cWBC may be related to apoptosis induction, as evidenced by typical apoptotic morphology features. Moreover, certain cWBC concentrations induced significant overproduction of ROS and significantly inhibited the $S-G_2/M$ transition in the cancer cell. The molecular mechanisms of cWBC in apoptosis induction were to decrease Bcl-2 and XIAP expression levels and increase the expression levels of caspase-3, caspase-8, and p53. These led to a decrease in the expression level of the cell cycle-associated gene cyclin-B1 and the arrest of cell population growth. Consequently, these findings demonstrate the prospect of the use of cWBC for cancer therapy.

• 생명과학회지
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• 제26권7호
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• pp.805-811
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• 2016

본 연구에서는 동충하초 및 부추를 열수추출한 후, 최적배합비율을 선정하여 혼합 물추출물을 제조하고 이에 대한 이화학적 특성 및 생리활성 효능을 검증하고자 하였다. 동충하초 및 부추 혼합 물추출물을 제조하였을 때 소비자들이 가장 선호하는 비율은 70:30이었으며, 이취제거를 위한 첨가물로 10% 사과농축액을 사용하여 최종 혼합 물추출물을 제조하였다. 최적 혼합 물추출물의 이화학적 특성을 확인한 결과로 pH는 4.28±0.12로 약산성이었고, 총 산도는 0.19±0.05%로 나타났다. 당도와 탁도는 9.1°Brix 및 1.48을 나타내었다. 동충하초 및 부추 혼합 물추출물의 항산화능은 DPPH radical 소거능, 환원력 및 ABTS radical 소거능을 통하여 확인하였고, positive control와 유사하거나 다소 낮은 우수한 활성을 나타내었다. 또한, 동충하초 및 부추 혼합 물추출물을 LNCaP 및 RC-58T/h/SA#4 인체 전립선 암세포에 처리한 결과 1% 희석액부터 농도의존적으로 세포성장이 억제되는 경향이 나타났고, 형태학적 관찰에서도 농도의존적으로 세포의 형태학적 변화가 유도되는 것으로 확인되었다. 이상의 결과를 통하여 동충하초 및 부추 혼합 물추출물은 동충하초 단일추출물과 비교하여 항산화 및 암세포 성장 억제효능이 높은 것으로 나타나, 단일 추출물보다는 적합한 비율로 혼합한 추출물이 기능성음료를 제조할 때 높은 활성을 나타낼 것으로 판단된다.