• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5371-5376
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• 2015

Berberine (B1), isolated from stems of Coscinium fenestratum (Goetgh.) Colebr, was used as a principle structure to synthesize three phenolic derivatives: berberrubine (B2) with a single phenolic group, berberrubine chloride (B3) as a chloride counter ion derivative, and 2,3,9,10-tetra-hydroxyberberine chloride (B4) with four phenolic groups, to investigate their direct and indirect antioxidant activities. For DPPH assay, compounds B4, B3, and B2 showed good direct antioxidant activity ($IC_{50}$ values=$10.7{\pm}1.76$, $55.2{\pm}2.24$, and $87.4{\pm}6.65{\mu}M$, respectively) whereas the $IC_{50}$ value of berberine was higher than $500{\mu}M$. Moreover, compound B4 exhibited a better DPPH scavenging activity than BHT as a standard antioxidant ($IC_{50}=72.7{\pm}7.22{\mu}M$) due to the ortho position of hydroxyl groups and its capacity to undergo intramolecular hydrogen bonding. For cytotoxicity assay against human fibrosarcoma cells (HT1080) using MTT reagent, the sequence of $IC_{50}$ value at 7-day treatment stated that B1 < B4 < B2 ($0.44{\pm}0.03$, $2.88{\pm}0.23$, and $6.05{\pm}0.64{\mu}M$, respectively). Berberine derivatives, B2 and B4, showed approximately the same level of CAT expression and significant up-regulation of SOD expression in a dose-dependent manner compared to berberine treatment for 7-day exposure using reverse transcription-polymerase chain reaction (RT-PCR) assays. Our findings show a better direct-antioxidant activity of the derivatives containing phenolic groups than berberine in a cell-free system. For cell-based system, berberine was able to exert better cytotoxic activity than its derivatives. Berberine derivatives containing a single and four phenolic groups showed improved up-regulation of SOD gene expression. Cytotoxic action might not be the main effect of berberine derivatives. Other pharmacological targets of these derivatives should be further investigated to confirm the medical benefit of phenolic groups introduced into the berberine molecule.

• 대한본초학회지
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• 제23권1호
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• pp.1-8
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• 2008

Objectives : The purpose of this study was to investigate extracts from mixed culture of Oriental medicines and cereal medium and mycelia of Trichloma matsutake and Cordyceps militaris by fermentation to develop new material for pharmaceutical products and medicinal food, Methods : To evaluate physiological activities of OCM extracts, we examined antioxidant activity(total polyphenol contents, electronic donating ability, SOD-like activity), ${\beta}$-glucan contents, nitric oxide production and cytotoxicity by MTT assay. Results : Total polyphenol contents of fermented OCM(UF) and non-fermented OCM(UM) extracts were more than 40% UM and UF of DPPH radical scavenging activity was 25.67%, 23.43% respectively. Total polyphenol content of non-fermented extract (UME) was 12.57%, while that of fermented extract(UFE) was 7.05%. SOD like activity showed UM 85.35%, UF 76.18%, UME 58.42%, UFE 72.21%. UME, and UFE 31.43%, ${\beta}$-glucan contents of UME and UFE were more than 40%. NO productions of UME, and UFE showed a LPS dose dependent tendency. Cytotoxicity on Raw 264.7 cell showed more than 90% viability. Inhibitory effect of UFE on HT1080 cell growth was higher than UME. Conclusions : These results showed that extracts from mixed culture of mushroom mycelium and OCM have physiological activities which can be used in pharmaceutical products and medicinal food.

• 혜화의학회지
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• 제9권2호
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• pp.97-109
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• 2001

To evaluate the antitumor activity and antimetastatic effects of HDBT, studies were done experimentally. The results were obtained as follows: 1. HDBT extracts didn't show cytotoxicity against BALB/C mouse lung fibroblast cell. 2. In cytotoxicity against A549, SK-OV-3, B16-BL6 and HT1080 concen- tration inhibiting cell growth up to below 30% of control was recognized at $10^{-3}g/ml$ of HDBT. 3. The concentration inhibiting adhesion of A549 and B16-BL6 to complex extracellular matrix up to below 30% of control was recognized at $10^{-3}g/ml$ of HDBT. 4. In Inhibitory effect on activity of DNA topoisomerase I, the $IC_{50}$ was shown $200-300{\mu}g/m{\ell}$ of HDBT. 5. The T/C% was 137.9% in HDBT-treated group in S-180 bearing ICR mice. 6. In CAM assay, HDBT extracts inhibited angiogenesis significantly at $15{\mu}g/egg$ concentration as compared with control. 7. In pumonary colonization assay, a number of colonies in the lungs were decreased but insignificantly in HDBT-treated group as compared with control group. 8. In hematological changes in B16-BL6 injected C57BL/6, numbers of WBC were decreased significantly in HDBT-treated group but numbers PLT were increased insignificantly as compared with control. From above results it was concluded that HDBT could be usefully applied for the prevention and treatment of cancer.

• 한국식품과학회지
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• 제32권6호
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• pp.1371-1378
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• 2000

S. typhimurium TA98과 TA100을 이용한 Ames test에서는 아가리쿠스버섯 메탄올 추출물 모두 시료자체의 돌연변이원성은 없는 것으로 나타났다. 아가리쿠스버섯 메탄올 추출물$(200\;{\mu}g/plate)$ 중 TA98 균주를 이용한 항돌연변이 효과를 확인한 결과 직접변이원인 4NQO에 대해 92.4% 그리고 간접변이원인 Trp-P-1과 $B({\alpha})P$에 대해 각각 81.9%와 83.4%의 높은 억제효과를 나타내었다. 또한 TA100 균주에서 4NQO는 94.7%의 가장 높은 억제효과를 나타내었다. MNNG, Trp-P-1 및 $B({\alpha})P$은 각각 87.3%, 89.9% 그리고 92.3%의 억제율을 보였다. 각각의 변이원 물질에 대한 아가리쿠스버섯 분획물 $(200\;{\mu}g/plate)$의 항돌연변이 효과에서는 MNNG와 $B({\alpha})P$에 대해서는 분획물 모두가 80% 이상의 높은 억제율을 보였고, 4NQO는 TA98, TA100 두 균주 모두 에틸 아세테이트 분획물에서 95% 이상의 가장 높은 억제율을 나타내었다. 그리고 Trp-P-1에서는 TA98 균주에서 물층을 제외한 분획물이 높은 억제율을 나타내었고, TA100 균주에 대해서도 분획물 모두가 80% 이상의 높은 억제율을 나타내었다. 각종 암세포에 대한 아가리쿠스버섯 메탄올 추출물의 저해효과는 시료 1 mg/mL 투여시 MCF7 82.9%, A549 86.5%, HT1080 65.5%, Hep3B 84.3%, HeLa 91.9%, KAROIII 88.7% 그리고 K562세포에서는 82.0%의 억제효과를 나타내었다. 인간 정상 간세포 WRL68에 대한 시료 농도에 따른 세포독성효과는 1 mg/mL의 시료를 첨가시 50% 이하의 생육억제율을 나타냄으로써 정상세포에 대해서는 낮은 독성효과를 나타낸다는 사실을 알 수 있었다. 아가리쿠스버섯 분획물들에 대한 억제효과에서는 유방암 세포인 MCF7이 시료를 1 mg/mL 첨가하였을때 물층과 부탄올층을 제외한 분획물에서 90% 이상의 높은 억제효과를 보였다. 또한 에틸 아세테이트 분획물이 다른 분획물에 비해 각각의 암세포에 대해서도 1 mg/mL 첨가시 80% 이상의 높은 억제효과를 보였다. 그러나 물 분획물은 암세포에 대해 상대적으로 낮은 억제효과를 나타내었다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4601-4607
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• 2014

Red rice contains pharmacological substances including phenolics, oryzanol, tocotrienol and tocopherol. Recently, red rice extract has been employed as a source of antioxidants for inhibition of tumor growth. This study was carried out to evaluate the anti-invasion effects of red rice extract fractions on cancer cells. It was found that at $100{\mu}g/ml$ of crude ethanolic extract (CEE), hexane fraction (Hex) and dichloromethane fraction (DCM) could reduce HT1080 and MDA-MB-231 cancer cell invasion. Hex and DCM revealed higher potency levels than CEE, whereas an ethyl acetate fraction (EtOAc) had no effect. Gelatin zymography revealed that Hex decreased the secretion and activity of matrix metalloproteinase-2 and -9 (MMP-2 and-9). In contrast, the DCM fraction exhibited slightly effect on MMPs secretion and had no effect on MMPs activity. Collagenase activity was significantly inhibited by the Hex and DCM fractions. High amounts of ${\gamma}$-oryzanol and ${\gamma}$-tocotrienol were found in the Hex and DCM fractions and demonstrated an anti-invasion property. On the other hand, proanthocyanidin was detected only in the CEE fraction and reduced MDA-MB-231 cells invasion property. These observations suggest that proanthocyanidin, ${\gamma}$-oryzanol and ${\gamma}$-tocotrienol in the red rice fractions might be responsible for the anti invasion activity. The red rice extract may have a potential to serve as a food-derived chemotherapeutic agent for cancer patients.

• Nutritional Sciences
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• 제7권3호
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• pp.144-150
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• 2004

We have investigated the effect of calcium spirulan(Ca-SP) isolated from a blue-green alga Spirulina platensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose and fructose, on invasion of both B16- BL6 melanoma cells, Colon 26 carcinoma and HT-1080 fibrosarcoma cells through reconstituted basement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells through Matrigel/fibronectin-coated filters in a concentration-dependent manner. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin, but it had no inhibitory effect on tumor cell migration to fibronectin-coated filters. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel- and laminin-substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells with Ca-SP inhibited the adhesion to laminin in a concentration-dependent fashion, while the pretreatment of laminin-substrates did not. Ca-SP had no effect on the production and activation of type IV collagenase in gelatin zymography. In contraset, Ca-SP significantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lung metastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP in a dose-dependent manner. Seven intermittent ⅰ.ⅴ. injection of 100$\mu\textrm{g}$ of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, could reduce the lung colonization of B16-BL6 melanoma cells in experimental metastasis model, by inhibiting the tumor invasion of basement membrane Matrigel, probably through the prevention of the adhesion and migration of tumor cells to laminin-substrate and of the heparanase activity.

• 농업과학연구
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• 제36권1호
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• pp.41-50
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• 2009

Fucoidan is a uniquely-structured sulfated fucose-rich polysaccharide derived from brown algae. Recently, the abalone glycosidase-digested fucoidan extract (fucoidan extract) derived from seaweed Cladosiphon novae-caledoniae Kylin (Mozuku) draws much attention because of its clinical anti-cancer effect in Japan. Here, we report the cancer cells-specific apoptosis inducing effects of the fucoidan extract. The fucoidan extract suppressed the growth of various anchorage-dependent and -independent cancer cells. The fucoidan extract contained low molecular weight components, which induced apoptosis of human leukemic HL 60 cells but not of human lymphocytes. It was shown that the fucoidan extract lead caspase 3/7 activation and loss of mitochondrial membrane potential in HL 60 cells. Another function of the fucoidan extract was also observed. It has been known that sugar chain expression on the surface of cancer cell membrane changes dependent on their malignancy. The analysis on sugar chain expression profiling using FITC-labeled lectins revealed that the expression of concanavalin A (Con A) binding sugar chain was enhanced by the treatment of human lung adenocarcinoma A549, human uterine carcinoma HeLa and human fibrosarcoma HT1080 cells with the fucoidan extract. Con A-induced apoptosis of cancer cells was stimulated in a dose-and time-dependent manner by the treatment with the fucoidan extract but not of human normal fibroblast TIG-1 cells.

• Archives of Pharmacal Research
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• 제28권11호
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• pp.1270-1274
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• 2005

The vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, which is a process where new blood vessels develop from the endothelium of a pre-existing vasculature. VEGF exerts its activity by binding to its receptor tyrosine kinase, KDR/Flk-1, which is expressed on the surface of endothelial cells. A methanol extract and organic solvent (n-hexane, ethyl acetate, n-butanol, aqueous) fractions from Rubus coreanus were examined for their inhibitory effects on VEGF binding to the VEGF receptor. The methanol extract from the crude drug were found to significantly inhibit VEGF binding to the VEGF receptor ($IC_{50}$$\thickapprox$27 $\mu$g/mL). Among the fractions examined, the aqueous fraction from the medicinal plant showed potent inhibitory effects against the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ in a dose­dependent manner ($IC_{50}$$\thickapprox$11 $\mu$g/mL). Sanguiin H-6 was isolated as an active principle from the aqueous fraction, and inhibited the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ in a dose­dependent manner ($IC_{50}$$\thickapprox$0.3 $\mu$g/mL). In addition, sanguiin H-6 efficiently blocked the VEGF­induced HUVEC proliferation in a dose-dependent manner ($IC_{50}$$\thickapprox$7.4 $\mu$g/mL) but had no effect on the growth of HT1080 human fibrosarcoma cells. This suggests that sanguiin H-6 might be a potential anti-angiogenic agent.

• 생명과학회지
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• 제16권7호
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• pp.1080-1086
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• 2006

본 연구에서는 해조류의 항돌연변이 및 항암 생리활성물질을 검색하여 발암물질 생성 방지 및 생체 방어 물질로서의 이용 가능성을 검토하고자 Ames test를 이용하여 직접돌연변이원인 MNNG와 간접돌연변이원인 $AFB_1$에 대한 항돌연변이 효과 및 암세포 증식 억제 효과를 알아보고자 하였다. $AFB_1$에 대해서 괭생이모자반(S. horneri)이 실험에 사용된 다른 해조류들 중에서 가장 높은 돌연변이 억제 효과를 보였다. 첨가농도 1.25mg/plate일 때, 괭생이모자반의 acetone+methylene chloride 추출물과 methanol 추출물은 각각 96%, 91%로 실험에 사용된 다른 해조류들의 추출물들 중에서 가장 높았으며 양성 대조군인 다시마의 용매 추출물보다도 높은 돌연변이 억제 효과를 보였다. $AFB_1$과 같은 농도인 0.6mg/plate의 농도의 MNNG를 사용하여 S. typhimurium TA100 균주에 대한 해조류의 항돌연변이성 실험을 한 결과, 간접 돌연변이원인 $AFB_1$에 비해 직접 돌연변이원인 MNNG에 대해서는 다소 항돌연변이 효과가 떨어지지만, 여기서도 실험에 사용된 해조류들의 돌연변이 억제 효과를 살펴볼 수 있었으며 acetone+methylene chloride 추출물의 경우가 methanol 추출물보다 다소 높은 활성을 나타내었다. 항돌연변이 실험에서 효과가 뛰어난 괭생이모자반과 짝잎모자반을 중심으로 인체 암세포(위암세포, AGS 및 결장암 세포, HT-29) 증식억제효과를 살펴본 결과, 용매 추출물을 0.5%, 1% 및 2%의 농도별로 암세포에 처리했을 때 acetone+methylene chloride 추출물과 methanol 추출물은 둘 다 가장 낮은 농도인 0.5%에서부터 농도 의존적으로 암세포 증식 억제 효과가 증가하였다. 이상의 7종의 갈조류 추출물들은 Ames test에서 높은 항돌연변이 효과를 나타냈을 뿐만 아니라 괭생이모자반 및 짝잎모자반은 인체 암세포에 대해서도 높은 증식 억제 효과를 나타냄을 살펴 볼 수가 있었다.

• 동의생리병리학회지
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• 제17권4호
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• pp.969-979
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• 2003

Gamisoamsan is a prescription originated in Soamsan which is known as an anti-cancer remedy in the traditional Korean Medicine. To enhance the synergic effects of anti-cancer activity of Soamsan, this study reconstituted the original components of Soamsan with a slight modification and produced a novel herbal remedy, namely Gamisoamsan. To investigate the effects of Gamisoamsan on anti-cancer reaction, I studied the effects of Gamisoamsan on angiogenesis via chorioallantoic membrane (CAM) assay, corneal neovascularization assay and the effects on expression of growth factor which are VEGF, TGF-β, bFGF and IMUP-1. Anti-cancer effects of Gamisoamsan was also abserved through hematological parameters, tumor volume and survival rate in mice. Gamisoamsan inhibited embryonic angiogenesis of blood vessels in CAM assay and inhibited neovascularization of ral cornea. Gamisoamsan reduced cell proliferation in HT1080 cells and IC50 was 2.18 ㎎/㎖ Gamisoamsan reduced the expression of VEGF, TGF-β, bFGF and IMUP-1 which was known as vascular growth factor and this effects of Gamisoamsan was predominant than VP-16. The treatment of Gamisoamsan decreased the CT-26 cell inoculated-tumor volume in mice colon adenocarcinoma and increased mice survival which was inoculated CT-26 cells. The results of the present study suggest that Gamisoamsan extracts has a potential anti-tumor activity and may be an useful remedy to prevent and/or treat cancer.