• 한국자원식물학회지
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• 제26권6호
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• pp.673-677
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• 2013

In order to examine the effects of Korean cucurbitaceous plants on sonic hedgehog pathway and growth of cancer cells with over-activated hedgehog pathway, we measured the sonic hedgehog conditioned medium (shh-CM) induced alkaline phosphatase (ALP) activity and cell viability of pancreatic cancer cell lines by treatment of cucurbitaceous plants. Among the tested cucurbitaceous plants, Actinostemma lobatum Maxim, Cucumis sativus L., Momordica charantia L., Schizopepon bryoniaefolius Maxim and Trichosanthes kirilowii Max, var. japonica Kitam showed the potent inhibitory effects (> 50 % at $20{\mu}g/mL$) on shh-CM induced ALP activity. We also evaluated the cell viability of pancreatic cancer cells treated with the cucurbitaceous plants. The tested cucurbitaceous plants showed the very weak effects on cancer cell proliferation but, T. kirilowii Max, var. japonica Kitam presented the inhibitory effect of 72.7 % on the proliferation of pancreatic cancer cells at $20{\mu}g/mL$. Taken together, we screened the effects of Korean cucurbitaceous plants on shh-CM induced ALP activity and cell viability of pancreatic cancers to search for the modulators of the hedgehog pathway leading to the inhibition of cancer cell proliferation. T. kirilowii Max, var. japonica Kitam, among the tested cucurbitaceous plants, showed the inhibitory effects on the shh-CM induced ALP activity and the proliferation of pancreatic cancer cells.

• 대한본초학회지
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• 제21권1호
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• pp.71-77
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• 2006

Objectives : This investigation was undertaken to evaluate the anti-proliferation of CURCUMAE LONGAE Rhizoma extracts using MCF-7, human breast cancer cells. Methods : MCF-7 cells were cultured in Dulbecco's modified Eagle's medium/F12 supplemented with 10% fetal bovine serum and antibiotics. At varying times after extract treatment, cells were harvested with scraper and processed for analysis of proliferation, cytotoxicity. Results : The extract of CURCUMAE LONGAE Rhizoma strongly inhibits the proliferation of MCF-7 cells in a dose and time-dependent manner. Sulforhodamine B assay showed that the addition of ethanol extract of CURCUlVIAE LONGAE Rhizoma reduced the viability of MCF-7 cells in a dose-dependent manner. Conclusion : So, it can be concluded that CURCUMAE LONGAE Rhizoma have an inhibitive effect on MCF-7 human breast cancer cells.

• Parasites, Hosts and Diseases
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• 제55권5호
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• pp.491-503
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• 2017

The effects of tyrosine kinase inhibitors (TKIs) were evaluated on growth inhibition of intracellular Toxoplasma gondii in host ARPE-19 cells. The number of tachyzoites per parasitophorous vacuolar membrane (PVM) was counted after treatment with TKIs. T. gondii protein expression was assessed by western blot. Immunofluorescence assay was performed using Programmed Cell Death 4 (PDCD4) and T. gondii GRA3 antibodies. The TKIs were divided into 3 groups; non-epidermal growth factor receptor (non-EGFR), anti-human EGFR 2 (anti-HER2), and anti-HER2/4 TKIs, respectively. Group I TKIs (nintedanib, AZD9291, and sunitinib) were unable to inhibit proliferation without destroying host cells. Group II TKIs (lapatinib, gefitinib, erlotinib, and AG1478) inhibited proliferation up to 98% equivalent to control pyrimethamine ($5{\mu}M$) at $20{\mu}M$ and higher, without affecting host cells. Group III TKIs (neratinib, dacomitinib, afatinib, and pelitinib) inhibited proliferation up to 98% equivalent to pyrimethamine at $1-5{\mu}M$, but host cells were destroyed at $10-20{\mu}M$. In Group I, TgHSP90 and SAG1 inhibitions were weak, and GRA3 expression was moderately inhibited. In Group II, TgHSP90 and SAG1 expressions seemed to be slightly enhanced, while GRA3 showed none to mild inhibition; however, AG1478 inhibited all proteins moderately. Protein expression was blocked in Group III, comparable to pyrimethamine. PDCD4 and GRA3 were well localized inside the nuclei in Group I, mildly disrupted in Group II, and were completely disrupted in Group III. This study suggests the possibility of a vital T. gondii TK having potential HER2/4 properties, thus anti-HER2/4 TKIs may inhibit intracellular parasite proliferation with minimal adverse effects on host cells.

• BMB Reports
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• 제43권4호
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• pp.291-296
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• 2010

Cyclin-dependent kinase 2 (CDK2) is a member of serine/threonine protein kinases, which initiates the principal transitions of the eukaryotic cell cycle and is a promising target for cancer therapy. The present study was designed to inhibit cdk2 gene expression to induce cell cycle arrest and cell proliferation suppression. Here, we constructed a series of RNA interference (RNAi) plasmids which can successfully express small interference RNA (siRNA) in the transfected human cells. The results showed that the RNAi plasmids containing the coding sequences for siRNAs down-regulated the cdk2 gene expression in human cancer cells at the mRNA and the protein levels. Furthermore, we found that the cell cycle was arrested at G0G1 phases and the cell proliferation was inhibited by different siRNAs. These results demonstrate that suppression of CDK2 activity by RNAi may be an effective strategy for gene therapy in human cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2967-2971
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• 2012

Objective: To explore whether monoclonal antibodies against stathmin and the chemotherapuetic agent paclitaxel have synergenic effects in inhibiting growth and inducing apoptosis in human QG-56 cells. Methods: QG-56 cells were treated with monoclonal antibodies against stathmin or paclitaxel alone or in combination, with untreated cells used as controls. After 24, 48, 72 and 96 hours the cell growth condition was observed under an inverted microscope and inhibition was studied by MTT assay; apoptosis was analyzed by flow cytometry. Results: The populations decreased and cell shape and size changed after the various treatments. Monoclonal antibodies against stathmin and paclitaxel used alone or incombination inhibited the proliferation of QG-56 cells, especially in combination with synergism (P<0.05). Combined treatment also resulted in a significantly higher apoptosis rate than in the other groups (P<0.05). Conclusions: Monoclonal antibodies against stathmin and paclitaxel used alone or in combination can inhibit proliferation of QG-56 cells and induce apoptosis when applied together. The observed synergistic effects may have important implications for clinical application.

• Preventive Nutrition and Food Science
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• 제19권4호
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• pp.299-306
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• 2014

Hesperetin has been shown to possess a potential anti-angiogenic effect, including vascular formation by endothelial cells. However, the mechanisms underlying the potential anti-angiogenic activity of hesperetin are not fully understood. In the present study, we evaluated whether hesperetin has anti-angiogenic effects in human umbilical vascular endothelial cells (HUVECs). HUVECs were treated with 50 ng/mL vascular endothelial growth factor (VEGF) to induce proliferation as well as vascular formation, followed by treatment with several doses of hesperetin (25, 50, and $100{\mu}M$) for 24 h. Cell proliferation and vascular formation were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and tube formation assay, respectively. In addition, cell signaling related to cell proliferation and vascular formation was analyzed by western blot. Furthermore, a mouse aorta ring assay was performed to confirm the effect of hesperetin on vascular formation. Hesperetin treatment did not cause differences in HUVECs proliferation. However, hesperetin significantly inhibited VEGF-induced cell migration and tube formation of HUVECs (P<0.05). Moreover, hesperetin suppressed the expression of ERK, p38 MAPK, and PI3K/AKT in the VEGF-induced HUVECs. In an ex vivo model, hesperetin also suppressed microvessel sprouting of mouse aortic rings. Taken together, the findings suggest that hesperetin inhibited vascular formation by endothelial cells via the inhibition of the PI3K/AKT, ERK and p38 MAPK signaling.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9131-9136
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• 2014

ELDF15, homologous with AT2 receptor-interaction protein 1 (ATIP1), may play an important role in cell differentiation, proliferation, and carcinogenesis. We aimed to understand the biological function of ELDF15 via construction and transfection of a recombinant expression vector containing antisense ELDF15. Recombinant expression vectors were successfully constructed and transfected into K562 cells. A stable transfectant, known as pXJ41-asELDF15, stably produced antisense ELDF15. Compared with K562 and K562-zeo cells, K562-pXJ41-asELDF15 cells showed inhibition of cell proliferation. RT-PCR analysis showed that the expression and protein level of ELDF15 decreased significantly in K562 cells transfected with pXJ41-asELDF15. Expression of hemoglobin increased in K562 cells transfected with pXJ41-asELDF15 by benzidine staining. increases NBT reduction activity in K562 cells transfected with pXJ41-asELDF15.Colony forming efficiency in two-layer soft agar was clearly inhibited as assessed by electron microscopy. These results suggest that ELDF15 plays a potential role in cell differentiation, proliferation and carcinogenesis.

• Journal of Ginseng Research
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• 제32권3호
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• pp.264-269
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• 2008

Ginsenosides are major components in Panax ginseng and known to have numerous pharmacological activities such as anti-cancer, anti-diabetes, anti-viral and anti-atherosclerosis effects. In this study, the regulatory activities of G-Rg3 and its derivative 25-hydroxy Rg3 (G-Rg3-2H) on the production of nitric oxide (NO) in macrophages and the proliferation of lymphocytes prepared from spleen and bone marrow under treatment of lipopolysaccharide (LPS) or concanavalin (Con) A were examined. G-Rg3 and G-Rg3-2H dose-dependently inhibited NO production from LPS-activated RAW264.7 cells and in agreement, these compounds protected RAW264.7 cells from LPS-mediated cytotoxicity. In contrast, G-Rg3-2H dose-dependently inhibited lymphocyte proliferation induced by both LPS and Con A, while there was no inhibition by G-Rg3. Therefore, our data suggest that these compounds may be applied for NO-mediated or lymphocyte-mediated immunological diseases.

• Journal of Dairy Science and Biotechnology
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• 제22권2호
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• pp.99-106
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• 2004

포자형성 유산균주에 대하여 종양세포에 대한 증식 억제 활성과 항산화 활성 및 세포내 glutathione 함유율을 측정하였다. 종양세포에 대한 억제활성은 균주에 따라 큰 차이를 나타내었고 Bacillus coagulans KTCC 3675는 높은 수준의 특이한 수준의 억제 활성을 나타내었고 human lymphoma cell NCLH-1299에 대한 억제 활성은 미약한 수준인 것으로 확인되었다. TBA 방법에 의한 linoleic acid에 대한 항산화 활성은 5~25% 정도의 항산화 활성을 보였고 특별히 높은 수준의 항산화 활성을 보인균주는 Bacillus coagulans KTCC 625, Bacillus coagulans KTCC 1015 및 Lactobacillus sporogens CU 815인 것으로 확인되었다. 포자형성 유산균체 추출액의 linoleic acid과산화 억제 활성과 세포내 glutathione함유율과의 상관계수는 0.78로서 고도의 유의성이 인정되는 상관계수를 나타내었다.

• 대한임상검사과학회지
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• 제49권4호
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• pp.329-336
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• 2017

본 연구는 포도수확 후 버려지는 가지를 이용한 포도전정가지 추출물(grape pruning stem extracts, GPSE)에 함유된 polyphenol류가 UVB로 유도된 HR-1 hairless mice의 손상된 피부에 대한 피부증식 억제, 항 알레르기, 아포토시스 억제능을 분석하여 기능성 화장품 소재로서의 응용 가능성을 확인하고자 하였다. 포도전정가지에서 polyphenol 성분을 80% 에탄올로 추출하고 여과하여 농축한 후, 동결건조하여 $-20^{\circ}C$에 보관하면서 사용하였다. GPSE의 유효성분 함량은 HPLC를 사용하여 선행연구논문에 보고하였다. 피부손상을 유도하기 위해 UVB를 HR-1 hairless mice에 조사하였고, GPSE가 피부 알레르기 반응을 일으키는지 확인하기 위하여 toluidine blue 염색을 통하여 비만세포의 수를 확인한 결과 포도전정가지 추출물(GPSE)를 도포한 그룹에서는 정상군과 유사한 결과를 나타내어 GPSE 도포군은 알레르기 반응이 없으며 suncream 대조군 대비 현저하게 감소하는 것을 확인할 수 있었다. 표피의 증식표지자인 PCNA 면역조직화학적 염색을 시행한 결과 GPSE와 serum base 혼합물의 모든 농도에서 대조군 대비 평균 42%로 표피상피세포 증식 억제 효과를 나타내었다. 또한 GPSE와 serum base 혼합물이 자외선 조사로 인한 아포토시스 억제율은 대조군 대비 평균 27% 억제 한다는 것을 알 수 있었다. 이상의 결과로 포도전정가지로부터 추출한 페놀성 화합물이 화장품 기초 원료인 serum base에 함유토록 제조된 GPSE는 피부증식 억제, 알레르기 억제, 아포토시스 억제효과를 얻을 수 있었다. 본 연구의 의의는 지역포도농가에서 수확 후 버려지는 포도전정가지에서 폴리페놀류와 같은 유효성분을 확보하여 고부가가치를 창출할 수 있는 기능성화장품 원료로서의 활용 가치가 높을 것으로 기대된다.