• Korean Journal of Acupuncture
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• 제18권1호
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• pp.11-20
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• 2001

댑싸리하고초 약침액을 이용하여 phase II detoxification 효소인 quinone reductase (QR 및 GST) 유도, GSH 생성량, phase I 효소 cytochrome P4501A1 활성억제, 발암물질 B[a]P-DNA adduct 형성의 저해효과 등을 측정하였다. QR 생성 유도를 Hepa1c1c7로 실험한 결과, 댑싸리하고초 약침액및 열수추출액 모두에서 유도 되었으며, 농도가 높아질수록 유도율이 더 높게 나타났으며, GSH와 GST의 유도율도 약침액에서 나타났다. 댑싸리하고초 약침액 $5{\times}$에서 45.2%의 cytochrome P4501A1 효소활성 저해효과를 측정할 수 있었다. 또한 B[a]P-DNA binding 저해효과를 실험한 결과, 약침액 $3{\times}$ 농도에서 45.0%의 저해효과가 있었다. 이상의 결과에 의하면 댑싸리하고초 약침액은 암억제 물질로서의 기능을 충분히 발휘할 것으로 사료된다.

• Journal of Ginseng Research
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• 제40권4호
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• pp.423-430
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• 2016

Background: The induction of cellular defensive genes such as phase II detoxifying and antioxidant enzymes is a highly effective strategy for protection against carcinogenesis as well as slowing cancer development. Transcription factor Nrf2 (nuclear factor E2-related factor 2) is responsible for activation of phase II enzymes induced by natural chemopreventive compounds. Methods: Red ginseng oil (RGO) was extracted using a supercritical $CO_2$ extraction system and chemical profile of RGO was investigated by GC/MS. Effects of RGO on regulation of the Nrf2/antioxidant response element (ARE) pathway were determined by ARE-luciferase assay, western blotting, and confocal microscopy. Results: The predominant components of RGO were 9,12-octadecadienoic acid (31.48%), bicyclo[10.1.0] tridec-1-ene (22.54%), and 22,23-dihydrostigmasterol (16.90%). RGO treatment significantly increased nuclear translocation of Nrf2 as well as ARE reporter gene activity, leading to upregulation of heme oxygenase-1 and NAD(P)H:quinone oxidoreductase 1. Phosphorylation of the upstream kinases such as apoptosis signal-regulating kinase (ASK)1, mitogen-activated protein kinase (MAPK) kinase (MKK)4/7, c-Jun N-terminal kinase (JNK), and p38 MAPK were enhanced by treatment with RGO. In addition, RGO-mediated Nrf2 expression and nuclear translocation was attenuated by JNK inhibitor SP600125 and p38 MAPK inhibitor SB202190. Conclusion: RGO could be used as a potential chemopreventive agent, possibly by induction of Nrf2/ARE-mediated phase II enzymes via ASK1-MKK4/7-JNK and p38 MAPK signaling pathways.

• 한국식품영양과학회지
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• 제44권4호
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• pp.592-601
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• 2015

복분자 와인의 제조를 위하여 복분자 과실 및 엑기스로부터 야생효모 Saccharomyces cerevisiae BA29를 분리 및 동정하였으며, 생화학적 특성 및 biogenic amine 생성 여부, 배양학적 특성 및 알코올 발효능과 알코올, 당, 아황산 저항성을 조사하였다. 또한 S. cerevisiae BA29의 산업적 공정 적용을 위한 균체량 증가를 위하여 통계학적 방법인 반응표면분석법을 사용하여 배양 배지 조성의 최적화를 수행하였다. 실험계획법은 중심합성계획을 사용하여 모델을 설정하였고, 산업적 공정 적용 시 비용 대비 효율성이 높은 molasses를 대체 탄소원으로 사용하여 실험을 수행하였다. 통계프로그램을 이용하여 분석한 결과 최대 균체 성장을 위한 배지 조성으로는 molasses 200 g/L, peptone 30 g/L, yeast extract 40 g/L로 예측되었으며, 이때의 최대 균체량은 20.6565 g/L로 예측되었다. 모델의 검증실험 결과 기본 배양 배지와 비교하였을 때 6.39 g/L에서 $20.9167{\pm}0.7925g/L$로 약 3.27배 증가하였다. 최종적으로 S. cerevisiae BA29를 사용하여 복분자 와인을 제조한 결과 20.33%의 알코올 생성능을 나타냈다. 이로써 복분자 과실로부터 분리한 효모 S. cerevisiae BA29를 이용한 우수한 복분자 와인 제조의 가능성을 확인하였다.

• 한국약용작물학회지
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• 제25권5호
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• pp.328-334
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• 2017

Background: In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of the root of Aralia cordata var. continentalis (Kitagawa) Y. C. Chu (RAc-E70) against human colorectal cancer cells. Methods and Results: RAc-E70 suppressed the proliferation of the human colorectal cancer cell lines, HCT116 and SW480. Although RAc-E70 reduction cyclin D1 expression at the protein and mRNA levels, RAc-E70-induced reduction in cyclin D1 protein level occurred more dramatically than that of cyclin D1 mRNA. The RAc-E70-induced downregulation of cyclin D1 expression was attenuated in the presence of MG132. Additionally, RAc-E70 reduced HA-cyclin D1 levels in HCT116 cells transfected with HA-tagged wild type-cyclin D1 expression vector. RAc-E70-mediated cyclin D1 degradation was blocked in the presence of LiCl, a $GSK3{\beta}$ inhibitorbut, but not PD98059, an ERK1/2 inhibitor and SB203580, a p38 inhibitor. Furthermore, RAc-E70 phosphorylated cyclin D1 at threonine-286 (T286), and LiCl-induced $GSK3{\beta}$ inhibition reduced the RAc-E70-mediated phosphorylation of cyclin D1 at T286. Conclusions: Our results suggested that RAc-E70 may downregulate cyclin D1 expression as a potential anti-cancer target through $GSK3{\beta}$-dependent cyclin D1 degradation. Based on these findings, RAc-E70 maybe a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.

• Food Science and Biotechnology
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• 제17권2호
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• pp.367-372
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• 2008

Cellular protection against carcinogens could be achieved by the induction of phase 2 detoxifying and antioxidant enzymes such as glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO1). Nuclear transcription factor E2-related factor 2 (Nrf2) binds to antioxidant response element (ARE) in the promoter region of these genes and the resulting transactivation occurs. In the present study the effect of gujeolcho (Chrysanthemum zawadskii) roots on the Nrf2-ARE pathway were investigated. C. zawadskii root extract was fractionated with a series of organic solvents and their ability to induce Nrf2-ARE pathway was examined. We separated the most potent dichloromethane (DCM) fraction into 12 sub-fractions and found several sub-fractions with strong effects on the Nrf2-ARE pathway. Fraction 4 strongly induced the ARE-reporter gene activity as well as Nrf2 expression. Sitosterol was isolated as a major compound in fraction 4 although its activity was not as potent as its mother fraction. These results indicate that C. zawadskii roots might be used as a potential natural chemopreventive source.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3735-3742
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• 2013

Background: Cardamom (Elettaria cardamom), also known as "Queen of Spices", has been traditionally used as a culinary ingredient due to its pleasant aroma and taste. In addition to this role, studies on cardamom have demonstrated cancer chemopreventive potential in in vitro and in vivo systems. Nevertheless, the precise poly-pharmacological nature of naturally occurring chemo-preventive compounds in cardamom has still not been fully demystified. Methods:In this study, an effort has been made to identify the proapoptopic, anti-inflammatory, anti-proliferative, anti-invasive and anti-angiogenic targets of Cardamom's bioactive principles (eucalyptol, alpha-pinene, beta-pinene, d-limonene and geraniol) by employing a dual reverse virtual screening protocol. Experimentally proven target information of the bioactive principles was annotated from bioassay databases and compared with the virtually screened set of targets to evaluate the reliability of the computational identification. To study the molecular interaction pattern of the anti-tumor action, molecular docking simulation was performed with Auto Dock Pyrx. Interaction studies of binding pose of eucalyptol with Caspase 3 were conducted to obtain an insight into the interacting amino acids and their inter-molecular bondings. Results:A prioritized list of target proteins associated with multiple forms of cancer and ranked by their Fit Score (Pharm Mapper) and descending 3D score (Reverse Screen 3D) were obtained from the two independent inverse screening platforms. Molecular docking studies exploring the bioactive principle targeted action revealed that H- bonds and electrostatic interactions forms the chief contributing factor in inter-molecular interactions associated with anti-tumor activity. Eucalyptol binds to the Caspase 3 with a specific framework that is well-suited for nucleophilic attacks by polar residues inside the Caspase 3 catalytic site. Conclusion:This study revealed vital information about the poly-pharmacological anti-tumor mode-of-action of essential oils in cardamom. In addition, a probabilistic set of anti-tumor targets for cardamom was generated, which can be further confirmed by in vivo and in vitro experiments.

• 한국식품영양학회지
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• 제28권1호
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• pp.111-118
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• 2015

이전 연구들에서 rutin과 quercetin을 포함한 여러 flavonoids의 암예방 활성이 보고되었으나, rutin의 경우 섭취 시 체내에서 HVA, HPAA, DHT라는 대사체로 변형되어 흡수된다. 그러나, 이들 대사체와 관련한 암예방 효능 및 그 분자생물학적 작용기작에 대한 연구 결과는 보고된 바가 없어, 본 연구에서 이를 규명하였다. DHT는 EGF로 유도된 세포 변형을 억제하였으며, AP-1 전사인자의 활성 또한 억제하였다. DHT는 Raf-1 효소 활성을 효과적으로 저해하므로서 MEK 및 ERK의 인산화를 억제하였으며, Raf-1과 ATP는 비경쟁적으로 직접 결합하여 Raf-1 효소 활성을 저해한다는 사실을 밝혀내었다. 이와는 대조적으로, rutin은 EGF로 유도된 세포 변형, AP-1 활성, ERK 신호전달체계, Raf-1 효소 활성을 억제하지 못하였다. 이상의 연구결과는 DHT의 암예방 활성이 발암과정과 밀접한 연관이 있는 Raf-1 효소 활성을 억제하여 세포 변형을 억제하는 것과 관련되어 있다는 것을 제시한다.

• Biomolecules & Therapeutics
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• 제15권2호
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• pp.95-101
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• 2007

Resveratrol (3,5,4’-trihydroxy-trans-stilbene), a naturally occurring phytoallexin abundant in grapes and several plants, has been shown to be active in inhibiting proliferation and inducing apoptosis in several human cancer cell lines. On the line of the biological activity of resveratrol, a variety of resveratrol analogs were synthesized and evaluated for their growth inhibitory effects against several human cancer cell lines. In the present study, we found that one of the resveratrol analogs, 3,4,5-trimethoxy-4’-bromo-cis-stilbene, markedly suppressed human colon cancer cell proliferation (EC$_{50}$ = 0.01 ${\mu}$g/ml), and the inhibitory activity was superior to its corresponding trans-isomer (EC$_{50}$ = 1.6 ${\mu}$g/ml) and resveratrol (EC$_{50}$ = 18.7 ${\mu}$g/ml). Prompted by the strong growth inhibitory activity in cultured human colon cancer cells (Col2), we investigated its mechanism of action. 3,4,5-Trimethoxy-4’-bromo-cis-stilbene induced arrest of cell cycle progression at G2/M phase and increased at sub-G1 phase DNA contents of the cell cycle in a time- and dose-dependent manner. Colony formation was also inhibited in a dose-dependent manner, indicating the inhibitory activity of the compound on cell proliferation. Moreover, the morphological changes and condensation of the cellular DNA by the treatment of the compound were well correlated with the induction of apoptosis. These data suggest the potential of 3,4,5-trimethoxy-4’-bromo-cis-stilbene might serve as a cancer chemotherapeutic or chemopreventive agent by virtue of arresting the cell cycle and inducing apoptosis for the human colon cancer cells.

• Toxicological Research
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• 제23권2호
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• pp.135-142
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• 2007

Formononetin is an isoflavonoid phytoestrogen found in certain foodstuffs such as soy and red clover. In this study, we examined the action of formononetin with the carcinogen activation pathway mediated through the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with formononetin alone caused the accumulation of CYP1A1 mRNA as well as elevation in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. However, a concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and formononetin markedly reduced both the DMBA-inducible EROD activity and CYP1A1 mRNA level. Under the same conditions, formononetin inhibited the DMBA-induced AhR transactivation, as shown by reporter gene analysis using a xenobiotic responsive element (XRE). Additionally, formononetin inhibited both DMBA-inducible nuclear localization of the aryl hydrocarbon receptor (AhR) and metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. Furthermore, formononetin competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. These results suggest that formononetin might be considered as a natural ligand to bind on AhR and consequently produces a potent protective effect against DMBA-induced genotoxicity. Therefore, that's the potential to act as a chemopreventive agent that is related to its effect on AhR pathway as antagonist/agonist.

• Nutrition Research and Practice
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• 제8권2호
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• pp.220-226
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• 2014

BACKGROUND/OBJECTIVES: Arsenic, which causes human carcinogenicity, is ubiquitous in the environment. This study was designed to evaluate modulation of arsenic induced cancer by resveratrol, a phytoalexin found in vegetal dietary sources that has antioxidant and chemopreventive properties, in arsenic trioxide ($As_2O_3$)-induced Male Wistar rats. MATERIALS/METHODS: Adult rats received 3 mg/kg $As_2O_3$ (intravenous injection, iv.) on alternate days for 4 days. Resveratrol (8 mg/kg) was administered (iv.) 1 h before $As_2O_3$ treatment. The plasma and homogenization enzymes associated with oxidative stress of rat kidneys were measured, the kidneys were examined histologically and trace element contents were assessed. RESULTS: Rats treated with $As_2O_3$ had significantly higher oxidative stress and kidney arsenic accumulation; however, pretreatment with resveratrol reversed these changes. In addition, prior to treatment with resveratrol resulted in lower blood urea nitrogen, creatinine and insignificant renal tubular epithelial cell necrosis. Furthermore, the presence of resveratrol preserved the selenium content ($0.805{\pm}0.059{\mu}g/g$) of kidneys in rats treated with $As_2O_3$. However, resveratrol had no effect on zinc level in the kidney relative to $As_2O_3$-treated groups. CONCLUSIONS: Our data show that supplementation with resveratrol alleviated nephrotoxicity by improving antioxidant capacity and arsenic efflux. These findings suggest that resveratrol has the potential to protect against kidney damage in populations exposed to arsenic.