• The Korean Journal of Food And Nutrition
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• v.28 no.6
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• pp.1090-1097
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• 2015

Traditionally, mistletoe is known as an effective anti-cancer medicinal plant, and lectin is recognized as a major component with cytotoxic and immuno-stimulant activity in mistletoe. A Korean mistletoe lectin (KML) has specificity to galactose and galactosamine and is distinguish from European mistletoe lectin (EML). When we examined the concentration of lectin in mistletoe originated from five different types of host trees, the result indicate that the lectin concentration is variable depending on the host tree. Noticeably, mistletoe from chestnut tree contains ten folds higher lectins than that of an oak tree. We also tested the concentration of KML and crude extract (KM-110) of Korean mistletoe that shows 90% cytotoxicity in L5178Y-ML25 lymphoma cell. In addition, the cells show 90% and 70% viability by the treatment of two neutralizing antibodies of KML, 9H7-D10 and 8B11-2C5 neutralization effect with two monoclonal antibodies of KML, 9H7-D10 and 8B11-2C5. Therefore, the result expected that the mistletoe contain some other cytotoxic components except lectin. Finally, the production of $TNF-{\alpha}$ and IL-6 by RAW 264.7 cells stimulated with lectin free-crude extract (LFKM-110) following neutralization by 9H7-D10 monoclonal antibody shows higher than that of lectin containing-crude extract (KM-110). These results suggest that the Korean mistletoe lectin ha a great potential to be developed as therapeutic agent of cancer.

• Food Science and Preservation
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• v.24 no.5
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• pp.673-679
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• 2017

In this study, the antimicrobial, antioxidant activities and ${\alpha}$-glucosidase inhibitory activities of Amphidinium carterae ethanol extract (AE) was evaluated for using as a functional food ingredient. Chlorella ethanol extract (CE) was used to the comparison as a control. Anticancer activities of the AE and CE were analyzed by HepG2 and HT-29 human cancer cell. The AE showed antimicrobial activities for all tested bacterial strains. Whereas, CE showed antimicrobial activities for several tested bacterial strains only. The CE showed higher total phenolics contents, DPPH and ABTS radical-scavenging activities (47.36 mg/g, 22.42% and 28.58%, respectively) than those of AE (8.88 mg/g, 20.16% and 17.69%, respectively). AE showed anti-diabetic effect on ${\alpha}$-glucosidase inhibitory activity with dose-dependantly manner. The cell viability of AE ($125{\mu}g/mL$) on HepG2 and HT-29 human cancer cells were 38.12% and 11.27%, respectively. It was demonstrated that ethanol was efficient solvent for extracting functional components from A. carterae. These results indicated that AE can be described as a good candidate for using as a functional food ingredient.

• Journal of Life Science
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• v.19 no.8
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• pp.1023-1032
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• 2009

Despite the fact that many cancer cells are sensitive to TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, some cancer cells show either partial or complete resistance to TRAIL. Human leukemic K562 and CEM cells also show resistance to TRAIL-induced apoptosis. Novel molecular target and treatment strategies are required to overcome TRAIL resistance of human leukemia cells. Therefore, the purpose of this study was to target key anti-apoptotic molecules deciding TRAIL resistance for sensitization of TRAIL-resistant K562 and CEM cells, and to evaluate the effect of quercetin as a TRAIL sensitizer on these TRAIL-resistant cells. We found that quercetin acted in synergy with TRAIL to enhance TRAIL-induced apoptosis in K562 cells by inhibition of the DNA-PK/Akt signaling pathway, which leads to enhancement of TRAIL-mediated activation of caspases and concurrent cleavage of PARP and up-regulation of Bax. The findings suggest that the DNA-PK/Akt signaling pathway plays an essential role in regulating cells to escape from TRAIL-induced apoptosis, and quercetin could act in synergy with TRAIL to increase apoptosis by inhibition of the DNA-PK/Akt signaling pathway, which overcomes TRAIL-resistance of K562 and CEM cells. This study suggests that DNA-PK might interfere with TRAIL-induced apoptosis in human leukemic cells through activation of the Akt signaling pathway.

• Journal of Life Science
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• v.26 no.2
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• pp.212-219
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• 2016

Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor in humans. Despite intensive treatment, including surgery, radiation, and chemotherapy, most patients die of the disease. Although the anti-cancer activity of resveratrol has been demonstrated in various cancer cell types, its underlying mechanism in glioma cells is not fully elucidated. The present study was undertaken to investigate the effect of resveratrol on cell viability and to determine the molecular mechanism in A172 human glioma cells. Resveratrol caused the generation of reactive oxygen species (ROS), and resveratrol-induced cell death was prevented by antioxidants (N-acetylcysteine and catalase), suggesting that an oxidative mechanism is responsible for resveratrol-induced cell death. Resveratrol-induced phosphorylation of extracellular signal-regulated kinase (ERK), p38 kinase, and c-Jun N-terminal kinase (JNK), and resveratrol-induced cell death were prevented by inhibitors of these kinases. Resveratrol-induced activation of caspase-3 and cell death were prevented by the caspase inhibitors. ERK activation and caspase-3 activation induced by resveratrol was blocked by N-acetylcysteine. Taken together, these results suggest that resveratrol causes a caspase-dependent cell death via activation of ERK, p38, and JNK, mediated by ROS generation, in human glioma cells.

• BMB Reports
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• v.54 no.11
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• pp.575-580
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• 2021

Cisplatin is widely known as an anti-cancer drug. However, the effects of cisplatin on mitochondrial function and autophagy-related proteins levels in the skeletal muscle are unclear. The purpose of this study was to investigate the effect of different doses of cisplatin on mitochondrial function and autophagy-related protein levels in the skeletal muscle of rats. Eight-week-old male Wistar rats (n = 24) were assigned to one of three groups; the first group was administered a saline placebo (CON, n = 10), and the second and third groups were given 0.1 mg/kg body weight (BW) (n = 6), and 0.5 mg/kg BW (n = 8) of cisplatin, respectively. The group that had been administered 0.5 mg cisplatin exhibited a reduced BW, skeletal muscle tissue weight, and mitochondrial function and upregulated levels of autophagy-related proteins, including LC3II, Beclin 1, and BNIP3. Moreover, this group had a high LC3 II/I ratio in the skeletal muscle; i.e., the administration of a high dose of cisplatin decreased the muscle mass and mitochondrial function and increased the levels of autophagy-related proteins. These results, thus, suggest that reducing mitochondrial dysfunction and autophagy pathways may be important for preventing skeletal muscle atrophy following cisplatin administration.

• The Journal of the Korean bone and joint tumor society
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• v.4 no.1
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• pp.13-21
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• 1998

Taxol, the extract from the Taxus brevifolia which is a Pacific yew tree has aroused the interest of the tumor investigators since the 1960s. As well, it is shown to have broad antitumor activity in preclinical experimental models. Its action mechanism is an anti-microtubule effect by duplication of tubulin. The most impressive antitumor activity of taxol has been observed in advanced ovarian cancer and metastatic breast cancer. The purpose of this study was to determine how taxol acts on malignant bone tumor cell lines, to compare its cytotoxic effect with those of other chemotherapeutic agents, and to ascertain the its combination effect with adriamycin. Cell lines used in this study were G-292(osteosarcoma, human), SaOS-2(osteosarcoma, primary, human), and HT-1080(fibrosarcoma, human). Methotrexate, adriamycin, cisplatinum, ifosfamide and taxol were used as testing chemotherapeutic agents and their maximum test concentration were $500{\mu}g/ml$, $200{\mu}g/ml$, $500{\mu}g/ml$, $1000{\mu}g/ml$, and $600{\mu}g/ml$, respectively. The media for cell culture was RPMI-1640 with 10% fetal bovine serum and gentamycin. The results were as follows. The $IC_{50}$ of methotrexate, ifosfamide, cisplatinum, adriamycin and Taxol in G-292 were $2.3{\times}10^{-1}{\mu}g/ml$, $8.0{\times}10^0{\mu}g/ml$, $3.5{\times}10^0{\mu}g/ml$, $9.8{\times}10^{-1}{\mu}g/ml$, $2.7{\times}10^{-2}{\mu}g/ml$ respectively, in SaOS-2 $3.5{\times}10^{-1}{\mu}g/ml$, $1.5{\times}10^1{\mu}g/ml$, $2.8{\times}10^0{\mu}g/ml$, $9.9{\times}10^{-2}{\mu}g/ml$, $1.0{\times}10^{-2}{\mu}g/ml$, respectively, in HT-1080 $4.2{\times}10^{-2}{\mu}g/ml$, $5.4{\times}10^1{\mu}g/ml$, $3.8{\times}10^0{\mu}g/ml$, $5.5{\times}10^{-3}{\mu}g/ml$, $1.1{\times}10^{-3}{\mu}g/ml$, respectively. In conclusion, taxol had very potent cytotoxic effect on the malignant bone tumor cell lines with adriamycin, and was more potent than methotrexate, cisplatinum and ifosfamide. There were synergistic antitumor effects on G-292 and SaOS-2 cell lines in combination test of taxol and adriamycin. From the above results, it would be estimated that taxol could be a new antitumor drug for the malignant bone tumors, providing measures against the side effects and followed by the clinical tests.

• Journal of Life Science
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• v.26 no.4
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• pp.439-445
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• 2016

Soybean leaves, a Korean edible plant material, have been reported to prevent the development of osteoporosis and breast cancer. Based on this rational, soybean fallen leaves ethanolic extract (SBFL) was used for the experiment of cell invasion related to metastasis and antioxidant activity. The effect of SBFL on matrix metalloproteinases (MMPs) in human fibrosarcoma cells, HT1080 as well as its anti-oxidant activity was investigated in this study. The effect of SBFL on scavenging activity of reactive oxygen species was evaluated in vitro using lipid peroxidation assay,DPPH radical and reducing power assay. SBFL showed the positive effects on antioxidant activity, compared with vitamin C and vitamin E used as positive controls. Furthermore, SBFL showed cytotoxicity above 16 µg/ml in MTT assay. In particular, it was found that SBFL decreased the activation of MMP-9 stimulated by phorbol 12-myristate 13-acetae (PMA) and phenazine methosulfate (PMS). SBFL treatment increased the expression levels of p-FoxO-1 and SOD-1. Moreover, SBFL inhibited cell invasion stimulated by vascular endothelial growth Factor (VEGF). These results indicate that SBFL could inhibit cell invasion related to the activation of MMP-9 and oxidative stress, suggesting that it could be available as a main ingredient for prevention of metastasis.

• The Korea Journal of Herbology
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• v.21 no.2
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• pp.37-46
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• 2006

Objectives : The purpose of this study was to investigate the effect of Dangguibohyultang (DB) and its combination (DB-I; Astragali membraneus BUNGE : Angelica gigas NAKAI=5:1, DB-II; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:1, DB-III; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:5,) on apoptosis in human colorectal adenocarcinoma HCT116 cells. Methods : To study the cytotoxic effect of methanol extract of DB-I, DB-II and DB-III on HCT116 cells, the cell viability was determined by XTT reduction method and ttypan blue exclusion assay. To confirm the induction of apoptosis, the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of procaspase-3, -8 and -9 were examined by western blot analysis. Furthermore, DB-induced apoptosis was confirmed by DNA fragmentation. The release of cytochrome C from mitochondria to cytosol, the level of Bcl-2 and Bax, and the expressions of Raf/MEK/ERK were examined by western blot analysis. Results : DB-I and DB-II reduced proliferation of HCT116 cells in a dose-dependent manner. DB-I and DB-II decreased procaspase-3, -8, -9 levels in a dose-dependent manner and induced the clevage of PARP. DB-I and DB-II also triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome C from mitochondria to cytosol, decreasing of anti-apoptotic Bcl-2, and increasing of pro-apoptotic Bax. DB-I and DB-II decreased the activation of Ras/Raf/MEK/ERK cascade in a dose-dependent manner. Conclusion : These results suggest that DB-I and DB-II induce apoptosis via mitochondrial pathway in HCT116 cells. Furthermore, Raf/MEK/ERK cascade is involved in DB-induced apoptosis. These results suggest that DB is potentially useful as a chemotherapeutic agent in human liver cancer.

• Molecular & Cellular Toxicology
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• v.5 no.2
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• pp.126-132
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• 2009

The usage and types of chemicals are advancing, specializing, large-scaled increasing, and new chemical exposed workers are concerning to occupational disease. The generation of reactive oxygen in the body from carcinogen, mutation and DNA damage in cancer is protected by natural antioxidants (phytochemicals) with antimutagenic effect. There were many reports of ginsenoside Rb$_1$, Rg$_1$ grievances of the genetic mutation to suppress the effect confirm the genetic toxicity test with chromosomal aberration test and the Comet (SCGE) assay confirmed the suppression effect occurring chromosomal DNA damage. We had wanted to evaluate the compatibility and sensitivity between the chromosomal aberration (CA) test and the Comet assay. We used the CA test and Comet assay to evaluate the anti-genotoxicity of ginsenoside Rb$_1$ and Rg$_1$, in CHO-K1 (Chinese hamster ovary fibroblast) cell in vitro, composed negative control (solvent), positive control (benzo[a]pyrene), test group (carcinogen+variety concentration of ginsenoside) group. The positive control was benzo[a]pyrene (50 $\mu$M), well-known carcinogen, and the negative control was the 1 % DMSO solvent. The test group was a variety concentration of ginsenoside Rb$_1$, Rg$_1$ with 10$^{-8}$%, 10$^{-6}$%, 10$^{-4}$%, 10$^{-2}$%, 1%, 10%. In chromo-somal aberration test, we measured the number of cells with abnormally structured chromosome. In Comet assay, the Olive tail moment (OTM) and Tail length (TL) values were measured. The ratio of cell proliferation was increased 8.3% in 10$^{-8}$%, 10$^{-6}$%, 10$^{-4}$%, 10$^{-2}$%, 1%, 10% Rb$_1$ treated groups, and increased 10.4% in 10$^{-10}$%, 10$^{-8}$%, 10$^{-6}$%, 10$^{-4}$%, 10$^{-2}$%, 1% Rg$_1$ treated groups. In the CA test, the number of chromosomal aberration was decreased all the Rb$_1$ and Rg$_1$ treated groups. In the Comet assay, the OTM values were decreased in all the Rb$_1$ and Rg$_1$ treated groups. To evaluate the compatibility between CA and Comet assay, we compared the reducing ratio of chromosomal abnormalities with its OTM values, it was identified the antimutagenicity of ginsenoside, but it was more sensitive the CA test than the Comet assay. Ginsenoside Rb$_1$ and Rg$_1$ significantly decrease the number of cells with chromosomal aberration, and decrease the extent of DNA migration. Therefore, ginsenoside Rb$_1$, Rg$_1$ are thought as an antioxidant phytochemicals to protect mutagenicity. The in vitro Comet assay seems to be less sensitive than the in vitro chromosomal aberration test.

• Food Science and Preservation
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• v.13 no.5
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• pp.649-654
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• 2006

To enhance beneficial effects of citron fruits, anticancer and antioxidant activities of citron fruits extracts were assessed with or without ascorbic acid. Total phenolic acids and flavonoids of fruits peels and flesh extracts were determined. Fruits peels contained more phenolic acids and flavonoids than those detected in flesh extracts. Scavenging activities of 1,1-diphenyl-2-picrylhydrazyl radicals and reducing powers were increased depending on the concentration. The antioxidant activities on oxidation of linoleic acid emulsion incubated at $50^{\circ}C$ were increased but the effect was small to that of butylated hydroxy toluene and ascorbic acid. The anti-tumorigenic effect of these compounds were investigated. They were shown to inhibit the in vitro proliferation of four human tumorigenic cell lines, HT-29, MCF-7, DU-145 and HepG2, in a doso-dependent manner. This study demonstrated that the antioxidant and anticancer activities of citron fruits extracts were derived from their phenols and flavonoids.