• International Journal of Oral Biology
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• 제35권4호
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• pp.153-158
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• 2010

Angelica decursiva has been used in Korean traditional medicine as an antitussive, an analgesic, an antipyretic and a cough remedy. However, the anti-cancer properties of Angelica decursiva have not yet been well defined. In our current study the cytotoxic activity of ethanol extracts of Angelica decursiva root (EEAD) and the mechanism of cell death exhibited by EEAD were examined in FaDu human head and neck squamous cell carcinoma cells. The cytotoxic effects of EEAD upon the growth of FaDu cells were examined with an MTT assay. In addition, the mechanism of cell death induced by EEAD was evaluated by DNA fragmentation analysis, immunoblotting and caspase activation measurements. EEAD induced apoptotic cell death in FaDu cells in a concentration- and time-dependent manner, as determined by MTT assay and DNA fragmentation analysis. Furthermore, the proteolytic processing of caspase-3, -7 and -9 was increased by EEAD treatment of FaDu cells. In addition, the activation of caspase-3 and -7 was detected in living FaDu cells by fluorescence microscopy. These results suggest that EEAD can induce apoptosis and suppress cell growth in cancer cells and may have utility as a future anticancer therapy.

• Preventive Nutrition and Food Science
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• 제11권3호
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• pp.184-190
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• 2006

Young radishes (YR, yeolmu in Korean) were cultivated in soil with and without sulfur. Control YR-kimchi and sulfur YR-kimchi were prepared using the young radishes cultivated in the soil without and with 1,818 $g/m^3$ sulfur, respectively. Fermentation of the YR-kimchis were conducted at $5^{\circ}C$ for 6 weeks. The control and sulfur YR-kimchis were reached pH 4.39 and pH 4.31 with 0.98% and 1.04% acidity at 5 weeks, respectively. At a higher concentration of 20 ${\mu}L/assay$, the sulfur YR-kimchi juice exhibited higher inhibitory effects (84%) on the growth of HT-29 human colon cancer cells than the control YR-kimchi (57%). Methanol extract from the YR-kimchis also led to similar results to those of the juices. In the inhibition study by hematocytometer, YR-kimchis inhibited the growth of cells in a time-dependent manner. Sulfur YR-kimchi induced apoptosis as determined by 4,6-diamidino-2-phenylindole (DAPI) staining and decreased Bcl-2 expression of active anticancer compounds, when compared to the control YR-kimchi. These results suggested that preparing kimchi using YR cultivated in the presence of sulfur, which can help to synthesize active compounds, could increase the anti-cancer activity of sulfur YR-kimchi.

• Journal of Ginseng Research
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• 제36권1호
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• pp.86-92
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• 2012

The glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Despite combination treatments of radiation and chemotherapy, the survival periods are very short. Therefore, this study was conducted to assess the potential of ginsenoside $F_2$ (F2) to treat GBM. In in vitro experiments with glioblastoma cells U373MG, F2 showed the cytotoxic effect with $IC_{50}$ of 50 ${\mu}g/mL$ through apoptosis, confirmed by DNA condensation and fragmentation. The cell population of cell cycle sub-G1 as indicative of apoptosis was also increased. In xenograft model in SD rats, F2 at dosage of 35 mg/kg weight was intravenously injected every two days. This reduced the tumor growth in magnetic resonance imaging images. The immunohistochemistry revealed that the anticancer activity might be mediated through inhibition of proliferation judged by Ki67 and apoptosis induced by activation of caspase-3 and -8. And the lowered expression of CD31 showed the reduction in blood vessel densities. The expression of matrix metalloproteinase-9 for invasion of cancer was also inhibited. The cell populations with cancer stem cell markers of CD133 and nestin were reduced. The results of this study suggested that F2 could be a new potential chemotherapeutic drug for GBM treatment by inhibiting the growth and invasion of cancer.

• Bulletin of the Korean Chemical Society
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• 제33권6호
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• pp.2005-2011
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• 2012

Nopp140 is a highly phosphorylated protein that resides in the nucleolus of mammalian cell and is involved in the biogenesis of the nucleolus. It interacts with a variety of proteins related to the synthesis and assembly of the ribosome. It also can bind to a ubiquitous protein kinase CK2 that mediates cell growth and prevents apoptosis. We found that Nopp140 is an intrinsically unfolded protein (IUP) lacking stable secondary structures over its entire sequence of 709 residues. We discovered that mitoxantrone, an anticancer agent, was able to enhance the interaction between Nopp140 and CK2 and maintain suppressed activity of CK2. Surface plasma resonance studies on different domains of Nopp140 show that the C-terminal region of Nopp140 is responsible for binding with mitoxantrone. Our results present an interesting example where a small chemical compound binds to an intrinsically unfolded protein (IUP) and enhances protein-protein interactions.

• 약학회지
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• 제49권1호
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• pp.38-43
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• 2005

The occurrence of resistance to chemotherapeutic drugs is a major problem for successful cancer treatment. This resistant phenotype of cancer cell frequently reveals a broad spectrum to structurally and/or functionally unrelated anticancer drugs, termed multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), a transmembrane drug efflux pump, is a major mechanism of MDR. Accordingly, considerable effort has been directed towards to development of compounds that inhibit P-gp, reverse the MDR phenotype and sensitize cancer cells to conventional chemotherapy without undesired toxicological effects. In an effort to search for novel MDR reversal agent, we tested the cytotoxicity of paclitaxel, a well-known substrate of P-gp, against P-gp-expressing HCT15 and HCT15/CL02 human colorectal cancer cells in the presence or absence of benzotriazepin analogues, as well as against P-gp-negative A549 human non-small cell lung and SK-OV-3 human ovarian cancer cells in vitro. Among the compounds tested, the agents that have phenyl amide moiety at 3 position remarkably increased the cytotoxicity of paclitaxel against P-gp-expressing cancer cells, but not against P-gp-negative cancer cells. BTZ-15 and BTZ-16 at $4\;{\mu}M$ revealed similar MDR reversal activity to $10\;{\mu}M$ verapamil, a well-known MDR reversal agent.

• Archives of Pharmacal Research
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• 제28권7호
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• pp.823-828
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• 2005

Multidrug resistance (MDR) is one of the most significant obstacles in cancer chemotherapy. One of the mechanisms involved in the development of MDR is the over-expression of P-glycoprotein (P-gp). It is widely known that natural compounds found in vegetables, fruits, plant-derived beverages and herbal dietary supplements not only have anticancer properties, but may also modulate P-gp activity. Therefore, the purpose of this investigation was to examine the effects of naturally occurring products on P-gp function in human breast cancer cell lines, MCF-7 (sensitive) and MCF-7/ADR (resistant). The accumulation of daunomycin (DNM), a P-gp substrate, was greater in the sensitive cells compared to the resistant cells, while the efflux of DNM was higher in the resistant cells compared to the sensitive cells over a period of 2h. The $IC_{50}$ value of DNM in the resistant cells was about 22 times higher than that in the sensitive cells, indicating an over-expression of P-gp in the resistant cells, MCF-7/ADR. All of the compounds tested, with the exception of fisetin, significantly decreased the $IC_{50}$ value of DNM. Biochanin A showed the greatest increase in $[^3H]-DNM$ accumulation, increasing by $454.3{\pm}19.5%$ in the resistant cells, whereas verapamil, the positive control, increased the accumulation by $229.4{\pm}17.6%$. Also, the accumulation of $[^3H]-DNM$ was increased substantially by quercetin and silymarin while it was reduced by fisetin. Moreover, biochanin A, silymarin, and naringenin significantly decreased DNM efflux from MCF-7/ADR cells compared with the control. These results suggest that some flavonoids such as biochanin A and silymarin may reverse MDR by inhibiting the P-gp function.

• Molecules and Cells
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• 제41권2호
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• pp.119-126
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• 2018

microRNA (miR)-612 shows anticancer activity in several types of cancers, yet its function in melanoma is still unclear. This study was undertaken to investigate the expression of miR-612 and its biological relevance in melanoma cell growth, invasion, and tumorigenesis. The expression and prognostic significance of miR-612 in melanoma were examined. The effects of miR-612 overexpression on cell proliferation, colony formation, tumorigenesis, and invasion were determined. Rescue experiments were conducted to identify the functional target gene(s) of miR-612. miR-612 was significantly downregulated in melanoma tissues compared to adjacent normal tissues. Low miR-612 expression was significantly associated with melanoma thickness, lymph node metastasis, and shorter overall, and disease-free survival of patients. Overexpression of miR-612 significantly decreased cell proliferation, colony formation, and invasion of SK-MEL-28 and A375 melanoma cells. In vivo tumorigenic studies confirmed that miR-612 overexpression retarded the growth of A375 xenograft tumors, which was coupled with a decline in the percentage of Ki-67-positive proliferating cells. Mechanistically, miR-612 targeted Espin in melanoma cells. Overexpression of Espin counteracted the suppressive effects of miR-612 on melanoma cell proliferation, invasion, and tumorigenesis. A significant inverse correlation (r = -0.376, P = 0.018) was observed between miR-612 and Espin protein expression in melanoma tissues. In addition, overexpression of miR-612 and knockdown of Espin significantly increased the sensitivity of melanoma cells to doxorubicin. Collectively, miR-612 suppresses the aggressive phenotype of melanoma cells through downregulation of Espin. Delivery of miR-612 may represent a novel therapeutic strategy against melanoma.

• 한국환경농학회지
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• 제34권3호
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• pp.217-222
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• 2015

BACKGROUND: Garlic (Allium sativum) contains polyphenols and sulfur compounds that are recognized as antioxidant, antithrombotic, anticancer, antibacterial, antimicrobial, nematicidal, and insecticidal activity. For this reason, the Environmentally-friendly Agriculture Promotion Act allowed the garlic extract as commercial biopesticide material for crop protection, nine commercial biopesticides containing A. sativum extract have been marketed in Korea. METHODS AND RESULTS: The determination of allylmethyl sulfide (AMS), dimethyl disulfide (DMDS), and dipropyl sulfide (DPS) in biopesticides containing A. sativum extract was developed and validated by gas chromatography (GC) mass spectrometry (MS) with head-space sampler. The developed method was validated, and the limit of quantification (LOQ) and recovery rates of AMS, DMDS, and DPS were 0.08, 0.32, and 0.09 mg/L and 90.3-91.3, 86.2-88.3, and 87.6-89.5%, respectively. From the nine commercial biopesticide samples, contents of AMS, DMDS, and DPS were analyzed using the developed method and results showed

• The Korean Journal of Physiology and Pharmacology
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• 제13권2호
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• pp.131-138
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• 2009

The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STA T3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2 a. The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.

• 동의생리병리학회지
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• 제20권5호
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• pp.1249-1253
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• 2006

The fractions of Capsosiphon fulvescens were studied to verify the anticancer and immunostimulating activity. The fractions from the ethanol extract of C. fulvescens were prepared by the systematic extraction procedure with the solvents such as hexane, ethyl ether, methanol, butanol and H$_2$O. The cytotoxic effects of C. fulvescens fractions against human leukemia cell line U937, mouse neuroblastoma cell line (NB41A3), human hepatoma cell line (HepG2)and rat glioma cell line (C6) were investigated. Ethyl ether fraction of C. fulvescens showed the highest cytotoxicity against all four cell lines tested. In addition, H$_2$O fraction also showed relatively high cytotoxicity. Dose dependent patterns were observed on all four cell lines. The immune-stimulating effects of C. fulvescens fractions on rat macrophage cell line (RAW 264.7) were also investigated. All five fractions of C. fulvescens extract stimulated NO production with concentration dependant manner. These results suggest that C. fulvescens may be a useful candidate for a natural antitumor and immune-stimulating agent.