• Journal of Life Science
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• v.17 no.12
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• pp.1634-1640
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• 2007

The 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS), nitric oxide (NO) scavenging activities and ferric- reducing/antioxidant power (FRAP) assay against extracts of Kalopanax pictus (KP) were measured. Radical scavenging and antioxidant activities were increased depend on the concentration and the effects were enhanced by ascorbic acid (AA). KP extracts and AA had a good anti-proliferating activity against HepG2 cells by MTT assay and induces cells apoptosis, which was demonstrated by flow cytometric analysis. KP extracts and AA caused the arrest of cell-cycle progression at either G0-G1-phase or G2/M-phase, which might be depending upon the KP extracts concentration. In addition, KP extracts and AA are effective in enhancing immunity and nitric oxide production by RAW 264.7 macrophages cells. KP extracts and AA inhibited tumor cell growth and exerted antioxidant effects as compared to controls. These results demonstrate that simultaneous AA and KP extracts treatment could be useful in preventing the oxidative damage and anti-proliferating HepG2 cells, and are effective in enhancing immunomodulatory and antioxidant activity.

• BMB Reports
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• v.34 no.3
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• pp.237-243
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• 2001

Taxol, a natural product extracted from the Taxus brevifolia, is known to have significant anti-tumor activities against many common cancers, including ovarian and breast cancers. Despite the pronounced anti-tumor activity of this compound, its poor solubility in aqueous solutions hampers its clinical applications. We studied the anticancer mechanisms of the water-soluble taxol diethylenetriamine pentaacetate (DTPA) used for radiolabeling, and compared it to that of taxol. In vitro cytotoxicities of taxol and taxol-DTPA conjugate were tested in HT29 human colorectal cancer cells by the MTT method. As the result, the $IC_{50}$ value of the taxol-DTPA conjugate was about three fold higher than that of taxol. When analyzed by an agarose gel electrophoresis, the DNA ladders became evident after the incubation of cells with the taxol-DTPA conjugate for 24 h. We also found morphological changes of the cells undergoing apoptosis with electron microscopy Next, we examined the signal pathway of taxol-DTPA conjugate-induced apoptosis in HT29 cells. The activation of extracellular signal-regulated protein kinase (ERK1/2) occurred at 10, 30, 60 and 120 min after 200 nM taxol-DTPA conjugate treatment. The pretreatment of the MEK inhibitor (PD98059) completely blocked the taxol-DTPA conjugate-induced ERK1/2 activation. The activated ERK1/2 translocated into the nucleus at the same time and phosphorylated its transcriptional factor, c-Jun. These results suggest that the taxol-DTPA conjugate has an apoptotic activity in HT29 cells, and that its proapoptic activity might be related with the signal transduction via ERK1/2 and c-Jun similar to that of taxol.

• Journal of Marine Bioscience and Biotechnology
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• v.1 no.2
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• pp.63-70
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• 2006

Natural product compounds are the source of numerous therapeutic agents. The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets including anticancer agents. Among these, pectenotoxin-2 (PTX-2), which was first identified as a cytotoxic entity in marine sponges, which depolymerizes actin filaments, was found to be highly effective and more potent to activate an intrinsic pathway of apoptosis in p53-deficient tumor cells compared to those with functional p53 both in vitro and in vivo. However, the anti-proliferative mechanism of the compound at non-cytotoxic concentrations has not yet been explored. In the current study, we sought to investigate anti-proliferation and apoptosis of PTX-2 against U937 human leukemic cells and its underlying molecular mechanism. Exposure of U937 cells to PTX-2 resulted in growth inhibition and induction of apoptosis in dose- and time-dependent manner as measured by MTT assay, fluorescent microscopy and flow cytometric analysis. The anti-proliferative effect of PTX-2 was associated with a marked increase in the expression of cyclin-dependent kinase p21 (WAF1/CIP1) mRNA which was tumor suppressor p53-independent. The increase in apoptosis was connected with a time-dependent down-regulation of anti-apoptotic Bcl-XL and inhibitor of apoptosis proteins (IAPs) family such as XIAP and cIAP-2. Though additional studies are needed, these findings suggested that PTX-2-induced inhibition of U937 cells was associated with the induction of apoptotic cell death and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of PTX-2.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.157.3-158
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• 2003

The antioxidant and anticancer properties of a medicinal plant, Betula platyphylla var. japonica were investigated. The total methanol extract of B. platyphylla var. japonica had protective effects against hydrogen peroxide ($H_2O_2$) in the Chinese hamster lung fibroblast (V79-4) cell line and induced apoptotic cell death in human promyelocytic leukemia (HL-60) cells, a cancer cell line. B. platyphylla var. japonica extract significantly increased cell viability against $H_2O_2$. The extract also showed high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity ($IC_50$ 2.4 mg/ml) and lipid peroxidation inhibitory activity ($IC_50$ below 4.0 mg/ml). (omitted)

• Journal of Life Science
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• v.17 no.8 s.88
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• pp.1121-1128
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• 2007

The fruits of Zanthoxylum piperitum are known as having various physiology vitality, and the abstraction ingredient of the pericarp is also known as having strong antibiotic activities against various bacteria. Therefore, this study was carried out to estimate the effect of physiology vitality when the abstraction ingredient of Z. piperitum was added in soy sauce(Chopi-kanjang) and soybean paste(Chopi-doenjang). For the antibiotic activity against the pathogens of sitotoxism such as Staphylococcus aureus, Salmonella typhimurium, Vibrio parahemolyticus, Escherichia coli 0157:H7, the extracts of the Chopi-kanjang was added 1%, 2%, 4% pericarp of Z. piperitum in the manufacturing process of soy source. According to the results, the growth of E. coli 0157:H7 and V. parahemolyticus were respectively inhibited as 70% and 50% by the Chopi-kanjang added 2% of the ingredient. For the antibiotic effects of the aforementioned Chopi-kanjang against Sal. typhimurium and Sta. aureus, the growth of those pathogens was also inhibited between 40% and 60% according to the manufacturing period of Chopi-kanjang. It was confirmed that the antibiotic activity using the mixture of the abstraction ingredient and Chopi-doenjang was lower than those of Chopi-kanjang. In order to estimate the anticancer activity using by caspase-3 activity, the mixture of the abstraction ingredient of the pericarp of Z. piperitum and Chopi-kanjang was treated to leukemia cells. According to the results, the activities of caspase-3 using the mixture added 1%, 2% and 4% of the abstraction ingredient were respectively increased as much as 4, 12, 15 times comparing with the control which was treated with the soy source only. It could be that the mixture of the abstraction ingredient of the pericarp of Z. piperitum and soy source induced apoptosis, and the mixture of the abstraction ingredient and soybean paste had no effect on the activity of caspase-3. In order to find out the death of the aforementioned cells caused by necrosis or apoptosis, DNA fragmentation in the cell was examined. U-937 cells showed apoptotic DNA fragmentation in the incubation with Chopi-kanjang extract.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.441-447
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• 2010

B13, a ceramide analogue, is a ceramidase inhibitor and induces apoptosis to give potent anticancer activity. A series of thiourea B13 analogues was evaluated for their in vitro cytotoxic activities against human renal cancer Caki-2 and leukemic cancer HL-60 in the MTT assay. Some compounds (12, 15, and 16) showed stronger cytotoxicity than B13 and C6-ceramide against both tumor cell lines, and compound (12) gave the most potent activity with $IC_{50}$ values of 36 and $9\;{\mu}M$, respectively. Molecular modeling of thiourea B13 analogues was carried out by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). We obtained highly reliable and predictive CoMSIA models with cross-validated $q^2$ values of 0.707 and 0.753 and CoMSIA contour maps to show the structural requirements for potent activity. These data suggest that the amide group of B13 could be replaced by thiourea, that the stereochemistry of 1,3-propandiol may not be essential for activity and that long alkyl chains increase cytotoxicity.

• Journal of Ginseng Research
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• v.39 no.1
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• pp.22-28
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• 2015

Background: Sun ginseng (SG), a specific formulation of quality-controlled red ginseng, contains approximately equal amounts of three major ginsenosides (RK1, Rg3, and Rg5), which reportedly has antitumor-promoting activities in animal models. Methods: MTT assay was used to assess whether SG can potentiate the anticancer activity of epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells; apoptosis status was analyzed by annexin V-FITC and PI and analyzed by flow cytometry; and apoptosis pathway was studied by analysis of caspase-3, -8, and -9 activation, mitochondrial accumulation of Bax and Bak, and cytochrome c release. Results: SG remarkably enhances cancer cell death induced by epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells. Results of the mechanism study highlighted the cooperation between SG and epirubicin or paclitaxel in activating caspase-3 and -9 but not caspase-8. Moreover, SG significantly increased the mitochondrial accumulation of both Bax and Bak triggered by epirubicin or paclitaxel as well as the subsequent release of cytochrome c in the targeted cells. Conclusion: SG significantly potentiated the anticancer activities of epirubicin and paclitaxel in a synergistic manner. These effects were associated with the increased mitochondrial accumulation of both Bax and Bak that led to an enhanced cytochrome c release, caspase-9/-3 activation, and apoptosis. Treating cancer cells by combining epirubicin and paclitaxel with SG may prove to be a novel strategy for enhancing the efficacy of the two drug types.

• Journal of Food Hygiene and Safety
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• v.27 no.4
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• pp.406-414
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• 2012

This study was designed to investigate the effect of fucoidan on the activation of macrophage and on induction of apoptosis in AGS cell. To measure the activity of macrophages, NO and TNF-${\alpha}$ assays were performed in Raw 264.7 cell. Treatment with fucoidan significantly increased production of NO and TNF-${\alpha}$, indicating activation of macrophages. The result of MTT assay shows that cell viability was significantly decreased in a dose and time-dependent manner. Fucoidan increased to enhance mitochondrial membrane permeability, as well as the cytochrome c release from the mitochondria. Fucoidan decreased Bcl-2 and XIAP expression, whereas the expression of Bax was increased in a time-dependent manner compared to the control. In addition, the active forms of caspase-9 were increased, and the inactivation of Akt was decreased in a time-dependent manner. Caspase inhibitor, z-VAD-FMK, canceled the apoptosis of fucoidan, expression of Bax and caspase-9 were decrease. These results indicate that fucoidan induces activation of macrophage and apoptosis through activation of caspase on AGS cell.

• Journal of Microbiology and Biotechnology
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• v.25 no.3
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• pp.334-342
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• 2015

4-O-Methylhonokiol (MH), a bioactive compound derived from Magnolia officinalis, is known to exhibit antitumor effects in various cancer cells. However, the precise mechanism of its anticancer activity in cervical cancer cells has not yet been studied. In this study, we demonstrated that MH induces apoptosis in SiHa cervical cancer cells by enhancing peroxisome proliferator-activated receptor-gamma (PPARγ) activation, followed by inhibition of the PI3K/Akt pathway and intrinsic pathway induction. MH upregulated PPARγ and PTEN expression levels while it decreased p-Akt in the MH-induced apoptotic process, thereby supporting the fact that MH is a PPARγ activator. Additionally, MH decreased the expression of Bcl-2 and Bcl-XL, inducing the intrinsic pathway in MH-treated SiHa cells. Furthermore, MH treatment led to the activation of caspase-3/caspase-9 and proteolytic cleavage of polyADP ribose polymerase. The expression levels of Fas (CD95) and E6/E7 oncogenes were not altered by MH treatment. Taken together, MH activates PPARγ/PTEN expression and induces apoptosis via suppression of the PI3K/Akt pathway and mitochondria-dependent pathways in SiHa cells. These findings suggest that MH has potential for development as a therapeutic agent for human cervical cancer.

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.80-89
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• 2022

The targeting of DNA methylation in cancer using DNA hypomethylating drugs has been well known to sensitize cancer cells to chemotherapy and immunotherapy by affecting multiple pathways. Herein, we investigated the combinational effects of DNA hypomethylating drugs and ionizing radiation (IR) in human sarcoma cell lines both in vitro and in vivo. Clonogenic assays were performed to determine the radiosensitizing properties of two DNA hypomethylating drugs on sarcoma cell lines we tested in this study with multiple doses of IR. We analyzed the effects of 5-aza-dC or SGI-110, as DNA hypomethylating drugs, in combination with IR in vitro on the proliferation, apoptosis, caspase-3/7 activity, migration/invasion, and Western blotting using apoptosis- or autophagy-related factors. To confirm the combined effect of DNA hypomethylating drugs and IR in our in vitro experiment, we generated the sarcoma cells in nude mouse xenograft models. Here, we found that the combination of DNA hypomethylating drugs and IR improved anticancer effects by inhibiting cell proliferation and by promoting synergistic cell death that is associated with both apoptosis and autophagy in vitro and in vivo. Our data demonstrated that the combination effects of DNA hypomethylating drugs with radiation exhibited greater cellular effects than the use of a single agent treatment, thus suggesting that the combination of DNA hypomethylating drugs and radiation may become a new radiotherapy to improve therapeutic efficacy for cancer treatment.