• Journal of Korean Traditional Oncology
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• v.20 no.2
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• pp.13-21
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• 2015

Objective : The objective of this study was to investigate the experimental efficacy of anti-tumor activity of the complexed herbal formula, Onbaekwon (OBW), which was derived from the literature of Traditional Korean Medicine, Dongeuibogam. Methods : Nine Cancer cell lines, LoVo, MCF-7, HepG2, AGS, A549, NCI-H69, HL-60, Sarcoma 180, LL/2, were prepared and the cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2yl)-2,5-dephenyl tetrazolium bromide (MTT) assay. Four of them, NCI-H69, HL-60, Sarcoma 180, and LL/2, showed strong cytotoxic activities and they were additionally undergone flow cytometry to find out their effects on apoptosis. ICR male mice were implanted with Sarcoma 180 intraperitoneally and divided into 8 species for each group. Control group was treated with normal saline, positive control group was treated with cyclophosphamide 8mg/kg, and experimental group was treated with OBW 1 g/kg. Results : Among 9 cancer cell lines, NCI-H69, HL-60, Sarcoma 180, and LL/2, expressed less than 0.10 mg/ml of $IC_{50}$ under 0.1~1mg/ml of OBW. NCI-H69, HL-60, Sarcoma 180, and LL/2, showed dose-dependent efficacy of apoptosis. When Sarcoma 180 cancer cell was implanted in ICR male mice and treated with the OBW, they prolonged the median overall survival for 0.8 days, from 17.5 to 18.3. Conclusion : OBW showed strong cytotoxicity to some cancer cells, which are NCI-H69, HL-60, Sarcoma 180, and LL/2, and its apoptotic activity was dose-dependent. OBW prolonged the median survival of mice implanted with Sarcoma 180. Further researches would be expected to support the efficacy of OBW.

• Journal of Korean Traditional Oncology
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• v.20 no.2
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• pp.5-11
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• 2015

Objective : The objective of this study was to investigate the anti-tumor activity of the complexed herbal formula, Haeamdan (HAD). Methods : Seven Cancer cell lines, LoVo, MCF-7, AGS, Sarcoma 180, HL-60, NCI-H69, LL/2, were prepared and the cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2yl)-2,5-dephenyl tetrazolium bromide (MTT) assay. HAD was applied with various concentrations from 0.1 to 1.0 mg/ml to figure out the appropriate dosage. ICR male mice were intraperitoneally implanted with Sarcoma 180 and divided into 8 species for each group. Control group was treated with normal saline, positive control group was treated with cyclophosphamide 8mg/kg, and experimental group was treated with HAD 1g/kg. Results : Among seven cancer cell lines, HAD exhibited strong cytotoxic activities to followed four cancer cell lines, that is, Sarcoma 180, HL-60, NCI-H69, and LL/2. These cytotoxic activity was expressed under 0.50 mg/ml of IC50 under 0.1~1mg/ml of OBW. When Sarcoma 180 cancer cell was implanted in ICR male mice and treated with the HAD, HAD prolonged the median overall survival for 3.6 days, from 17.5 to 21.1 days. Conclusion : HAD showed strong cytotoxicity to the cancer cells, Sarcoma 180, HL-60, NCI-H69, on in vitro study and it showed anti-tumor activity in vivo with the peritoneal cancer mice by prolonging the median survival for 3.6 days. Further researches would be expected to support the anti-tumor efficacy of HAD.

• Journal of Marine Bioscience and Biotechnology
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• v.2 no.2
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• pp.113-119
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• 2007

In this study, we investigated antimicrobial and cytotoxicity effects of Gelidium amansii L., which using methanol, dichloromethane and ethanol were extracted and fractionated into four different types : methanol (GAMM), hexane (GAMH), butanol (GAME) and aqueous (GAMA). The antimicrobial activity was increased in proportion to its concentration by the paper disc method. Among the solvent fractions, The methanol partition layer (GAMM) showed the strongest antimicrobial activities and cytotoxic effects on all cancer cell lines. We also observed quinone reductase (QR) induced effects in all fraction layers of GA on HepG2 cells. The QR induced effects of GAMM on HepG2 cells at $40{\mu}g/mL$ concentration indicated 2.5 with a control value of 1.0.

• Journal of Microbiology and Biotechnology
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• v.28 no.6
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.2
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• pp.148-153
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• 2008

We investigated the growth inhibitory effect of Salicornia herbacea L. (SH) on human cancer cell lines in vitro. SH was extracted with methanol (SHM), followed by further fractionation into four subfractions according to polarity: hexane (SHMH), methanol (SHMM), butanol (SHMB), and aqueous (SHMA) soluble fractions. We determined the growth inhibitory effect of these fractions against human cancer cell lines using MTT assay. Among the four subfractions of SHM, the SHMM showed the strongest cytotoxic effects on cancer cell lines. We also observed quinone reductase (QR)-inducing effect of methanol layer (SHMM) on HepG2 cells and it was determined to be 3.00 at $100\;{\mu}g/mL$ level compared to the control value of 1.0. The SHMM showed the highest induction activity of quinone reductase on HepG2 cells among the partition layers. The present work suggests that SH merits further study to confirm its chemopreventive potential.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.6
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• pp.765-770
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• 2005

In this study, we investigated antimicrobial and cytotoxicity effects of Undaria pinnatifida Sporophyll, which using methanol, dichloromethane and ethanol were extracted and fractionated into four different types: methanol (UPMM), hexane (UPMH), butanol (UPMB) and aqueous (UPMA). The antimicrobial activity was increased in proportion to its concentration by the paper disc method. Among the solvent fractions, UPMM and UPMB showed relatively strong antimicrobial activities in the order. Among various partition layers, the methanol partition layer (UPMM) was showed the strongest cytotoxic effects on all cancer cell lines. We also observed quinone reductase (QR) induced effects in all fraction layers of UP on HepG2 cells. The QR induced effects of UPMH on HepG2 cells at $320\mu g/mL$ concentration indicated 2.36 with a control value of 1.0.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.340-347
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• 2022

Advanced or metastatic breast cancer affects multiple organs and is a leading cause of cancer-related death. Cancer metastasis is associated with epithelial-mesenchymal metastasis (EMT). However, the specific signals that induce and regulate EMT in carcinoma cells remain unclear. PRR16/Largen is a cell size regulator that is independent of mTOR and Hippo signalling pathways. However, little is known about the role PRR16 plays in the EMT process. We found that the expression of PRR16 was increased in mesenchymal breast cancer cell lines. PRR16 overexpression induced EMT in MCF7 breast cancer cells and enhances migration and invasion. To determine how PRR16 induces EMT, the binding proteins for PRR16 were screened, revealing that PRR16 binds to Abl interactor 2 (ABI2). We then investigated whether ABI2 is involved in EMT. Gene silencing of ABI2 induces EMT, leading to enhanced migration and invasion. ABI2 is a gene that codes for a protein that interacts with ABL proto-oncogene 1 (ABL1) kinase. Therefore, we investigated whether the change in ABI2 expression affected the activation of ABL1 kinase. The knockdown of ABI2 and PRR16 overexpression increased the phosphorylation of Y412 in ABL1 kinase. Our results suggest that PRR16 may be involved in EMT by binding to ABI2 and interfering with its inhibition of ABL1 kinase. This indicates that ABL1 kinase inhibitors may be potential therapeutic agents for the treatment of PRR16-related breast cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.6
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• pp.862-873
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• 2015

In this study, we investigated the physiochemical properties and biological activities of Gangwon-do endemic Makjang (MJ) products (12 types). The pH levels of all samples were in the range of 4.43 to 5.69, and MJ5 showed the highest pH (5.69). The salinities of all samples ranged from 11.1% to 16.9%. Hunter color values for L (lightness), a (redness), and b (yellowness) ranged from 26.2 to 36.9, 3.9 to 11.5, and 6.5 to 16.6, respectively. The amino nitrogen content of MJ2 was highest, whereas the total content of free amino acids of MJ11 (4,657.7 mg%) was highest. Total fatty acid contents of all samples ranged from 1,598.6 mg% to 2,874.4 mg%, with MJ10 showing the highest fatty acid content. The content of total polyphenolic compounds ranged from 401.48 to $746.67{\mu}g$ tannic acid equivalent/mL, with MJ11 showing the highest content. The 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiozoline-6-sulfonic acid) radical scavenging effects of MJ11, MJ8, and MJ4 were 51.30% and 82.5%, 41.29% and 67.0%, and 49.88% and 87.7%, respectively. MJ12 showed the strongest growth inhibitory effect on lung cancer A549 cells, whereas MJ5 showed the strongest growth inhibitory effect on AGS gastric cancer cell and MCF-7 breast cancer cell. MJ7 showed greater lipid accumulation inhibitory activity in HepG2 cells than the others. ACE inhibitory activity of MJ11 was the highest among the samples.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05b
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• pp.88.2-98
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• 2002

A wide arry of naturally occurring substances particularly those present in dietary and medicinal plants, have been reported to possess substantial cancer chemopreventive properties. Certain phytochemicals retain strong antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activities. Inducible cyclooxygenase(COX-2) and nitric oxide synthase (iNOS) are important enzymes that mediate inflammatory processes. There is some evidence that expression of both COX-2 and iNOS is co-regulated by the eukaryotic transcription factor NF-$textsc{k}$B. Increased expression of COX-2 and/or iNOS has been associated with pathophysiology of certain types of human cancers as well as inflammatory diseases. Since inflammation is closely linked to tumor promotion, substances with potent anti-inflammatory activies are anticipated to exert chemopreventive effects on carcinogenesis, particularly in the promotion stage. An example is curcumin, a yellow pigment of turmeric (Curcuma longa L., Zingiberaceae), that strongly occurring diaryl heptanoids structurally related to curcumin have substantial anti-tumor promotional activities in two-stage mouse skin carcinogenesis. Thus, yakuchinone A [1-(4'-hydroxy-3'-methoxyphenyl)-7-phenyl-3heptanone] and yakuchinone B [1-(4'-hydroxy-3'methoxyphenyl)-7-phenylhept-1-en-3-one] present in Alpinia oxyphylla Miquel (Zingiberacease) attenuate phorbol ester-induced inflammation and papilloma formation in female ICR mice. These diarylheptanoids also suppressed phorbol ester-induced activation of epdermal ornithine decarboxylase and its mRNA expression when applied onto shaven backs of mice. Yakuchinone A and B as well as curcumin inhibited phorbol ester-induced expression of COX-2 and iNOS and their mRNA in mouse skin via inactivation of NF-$textsc{k}$B. Capsaicin, a major pungent ingredient of red pepper also attenuated phorbol ester-induced NF-$textsc{k}$B activation. Similar suppression of COX-2 and iNOS and down-regulation of NF-$textsc{k}$B activation for its DNA binding were observed with the ginsenosied Rg3 and the ethanol extract of Artemisia asiatica. We have also found that certain anti-inflammatory phytochemicals exert inhibitory effects on phorbol ester-induced COX-2 expression and NF-$textsc{k}$B activation in immortalized human breast epithelial (MCF-10A) cells in culture. One of the plausible mechanisms undelying inhibition by aforementioned phytochemicals of phorbol ester-induced NF-$textsc{k}$B activation involves interference with degragation of the inhibitory unit, I$textsc{k}$Ba, which blocks subsequent nuclear translocation of the functionally active p65 subunit of NF-$textsc{k}$B. the activation of epidermal NF-$textsc{k}$B by phorbol ester and subsequent induction of COX-2 hence appear to play an important role in intracellular signaling pathwasy leading to tumor promotion and targeted inhibition of NF-$textsc{k}$B may provide a new promising cancer chemopreventive strategy.

• Journal of Microbiology and Biotechnology
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• v.22 no.12
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• pp.1782-1789
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• 2012

We have developed a novel type of polymer nanogel loaded with anticancer drug based on bio-derived poly(${\gamma}$-glutamic acid) (${\gamma}$-PGA). ${\gamma}$-PGA is a highly anionic polymer that is synthesized naturally by microbial species, most prominently in various bacilli, and has been shown to have excellent biocompatibility. Thiolated ${\gamma}$-PGA was synthesized by covalent coupling between the carboxyl groups of ${\gamma}$-PGA and the primary amine group of cysteamine. Doxorubicin (Dox)-loaded ${\gamma}$-PGA nanogels were fabricated using the following steps: (1) an ionic nanocomplex was formed between thiolated ${\gamma}$-PGA as the negative charge component, and Dox as the positive charge component; (2) addition of poly(ethylene glycol) (PEG) induced hydrogen-bond interactions between thiol groups of thiolated ${\gamma}$-PGA and hydroxyl groups of PEG, resulting in the nanocomplex; and (3) disulfide crosslinked ${\gamma}$-PGA nanogels were fabricated by ultrasonication. The average size and surface charge of Dox-loaded disulfide cross-linked ${\gamma}$-PGA nanogels in aqueous solution were $136.3{\pm}37.6$ nm and $-32.5{\pm}5.3$ mV, respectively. The loading amount of Dox was approximately 38.7 ${\mu}g$ per mg of ${\gamma}$-PGA nanogel. The Dox-loaded disulfide cross-linked ${\gamma}$-PGA nanogels showed controlled drug release behavior in the presence of reducing agents, glutathione (GSH) (1-10 mM). Through fluorescence microscopy and FACS, the cellular uptake of ${\gamma}$-PGA nanogels into breast cancer cells (MCF-7) was analyzed. The cytotoxic effect was evaluated using the MTT assay and was determined to be dependent on both the concentration and treatment time of ${\gamma}$-PGA nanogels. The bio-derived ${\gamma}$-PGA nanogels are expected to be a well-designed delivery carrier for controlled drug delivery applications.