• 한국식품영양과학회지
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• 제40권5호
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• pp.649-659
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• 2011

연구에서는 콩다닥냉이 추출물의 항암활성을 조사하기 위하여 잎 및 뿌리의 열수 추출물(WELVL 및 WELVR)이 HCT116 대장암세포의 증식 억제와 연관된 apoptosis 유도 기전에 관한 연구를 시도하였다. 본 연구의 결과에 의하면 HCT116 세포에 WELVL 및 WELVR을 처리하였을 경우에 유발되는 증식 억제 및 형태 변화는 apoptosis 유발과 밀접한 연관이 있었으며, 증식억제 및 apoptosis 유도 효과는 WELVL에 비하여 WELVR에서 높게 나타났다. 특히 WELVR에 의한 apoptosis 유발에는 FasL의 발현 증가를 통한 caspase-8의 활성화와 이로 인한 Bid 단백질의 단편화와 함께 Bcl-2 family의 발현 변화를 통한 mitochondria의 기능 이상과 이로 인한 caspase-9 및 -3의 활성화, 그리고 기질단백질들의 분해가 중요한 역할을 하는 것으로 나타났다. 또한 IAP family의 발현 감소로 인한 caspase의 활성 증가도 어느 정도 관여하는 것으로 생각되어진다. 따라서 WELVR 처리에 의하여 유발되는 apoptosis는 extrinsic pathway 및 intrinsic pathway를 모두 경유하는 multiple apoptotic pathway에 의하여 조절되는 것으로 생각되며, 이러한 결과들은 인체 암세포에서 콩다닥냉이의 항암작용을 이해하는데 중요한 자료가 될 것이고 나아가 콩다닥냉이 추출물을 포함한 그와 유사한 항암제 후보물질들의 연구 기초자료로서 사용될 수 있을 것으로 생각된다.

• Nutrition Research and Practice
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• 제8권3호
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• pp.257-266
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• 2014

BACKGROUND/OBJECTIVE: Licorice has been shown to possess cancer chemopreventive effects. However, glycyrrhizin, a major component in licorice, was found to interfere with steroid metabolism and cause edema and hypertension. The roasting process of licorice modifies the chemical composition and converts glycyrrhizin to glycyrrhetinic acid. The purpose of this study was to examine the anti-carcinogenic effects of the ethanol extract of roasted licorice (EERL) and to identify the active compound in EERL. MATERIALS/METHODS: Ethanol and aqueous extracts of roasted and un-roasted licorice were prepared. The active fraction was separated from the methylene chloride (MC)-soluble fraction of EERL and the structure of the purified compound was determined by nuclear magnetic resonance spectroscopy. The anti-carcinogenic effects of licorice extracts and licochalcone A was evaluated using a MTT assay, Western blot, flow cytometry, and two-stage skin carcinogenesis model. RESULTS: EERL was determined to be more potent and efficacious than the ethanol extract of un-roasted licorice in inhibiting the growth of DU145 and MLL prostate cancer cells, as well as HT-29 colon cancer cells. The aqueous extracts of un-roasted and roasted licorice showed minimal effects on cell growth. EERL potently inhibited growth of MCF-7 and MDA-MB-231 breast, B16-F10 melanoma, and A375 and A2058 skin cancer cells, whereas EERL slightly stimulated the growth of normal IEC-6 intestinal epithelial cells and CCD118SK fibroblasts. The MC-soluble fraction was more efficacious than EERL in inhibiting DU145 cell growth. Licochalcone A was isolated from the MC fraction and identified as the active compound of EERL. Both EERL and licochalcone A induced apoptosis of DU145 cells. EERL potently inhibited chemically-induced skin papilloma formation in mice. CONCLUSIONS: Non-polar compounds in EERL exert potent anti-carcinogenic effects, and that roasted rather than un-roasted licorice should be favored as a cancer preventive agent, whether being used as an additive to food or medicine preparations.

• The Korean Journal of Physiology and Pharmacology
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• 제15권1호
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• pp.1-7
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• 2011

Many anticancer agents as well as ionizing radiation have been shown to induce autophagy which is originally described as a protein recycling process and recently reported to play a crucial role in various disorders. In HCT116 human colon cancer cells, we found that curcumin, a polyphenolic phytochemical extracted from the plant Curcuma longa, markedly induced the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II and degradation of sequestome-1 (SQSTM1) which is a marker of autophagosome degradation. Moreover, we found that curcumin caused GFP-LC3 formation puncta, a marker of autophagosome, and decrease of GFP-LC3 and SQSTM1 protein level in GFP-LC3 expressing HCT116 cells. It was further confirmed that treatment of cells with hydrogen peroxide induced increase of LC3 conversion and decrease of GFP-LC3 and SQSTM1 levels, but these changes by curcumin were almost completely blocked in the presence of antioxidant, N-acetylcystein (NAC), indicating that curcumin leads to reactive oxygen species (ROS) production, which results in autophagosome development and autolysosomal degradation. In parallel with NAC, SQSTM1 degradation was also diminished by bafilomycin A, a potent inhibitor of autophagosome-lysosome fusion, and cell viability assay was further confirmed that cucurmin-induced cell death was partially blocked by bafilomycin A as well as NAC. We also observed that NAC abolished curcumin-induced activation of extracelluar signal-regulated kinases (ERK) 112 and p38 mitogen-activated protein kinases (MAPK), but not Jun N-terminal kinase (JNK). However, the activation of ERK1/2 and p38 MAPK seemed to have no effect on the curcumin-induced autophagy, since both the conversion of LC3 protein and SQSTM1 degradation by curcumin was not changed in the presence of NAC. Taken together, our data suggest that curcumin induced ROS production, which resulted in autophagic activation and concomitant cell death in HCT116 human colon cancer cell. However, ROS-dependent activation of ERK1/2 and p38 MAPK, but not JNK, might not be involved in the curcumin-induced autophagy.

• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.254-261
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• 2007

20-O-($\beta$-D-Glucopyranosyl)-20 (S)-protopanaxadiol (IH-901) is one of the major metabolites of ginsenosides from Panax ginseng, and is suggested that IH-901 has been associated with various pharmacological and physiological activities. In this study, we demonstrate that IH-901 induced anti-inflammation in HT-29 human colon adenocarcinoma cells. Our results showed that IH-901 inhibited cell proliferation of HT-29 in a time- and dose-dependent manner. We also found that IH-901 was significantly decreased expression of iNOS compared with non-treated. We observed effect of IH-901 related with inflammatory genes using by cDNA microarray. We were known that the 34 inflammatory genes such as E2F, CDK6, TNF-$\alpha$, and PKC were down-regulated. Thus, these results suggest that IH-901 may have a potential preventive factor to improving cancer induced by chronic inflammation.

• 생명과학회지
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• 제28권6호
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• pp.733-737
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• 2018

박과 작물에 함유되어 있는 tetracyclic triterpene 성분 중 하나인 쿠쿠르비타신(cucurbitacin)-I는 대장암, 유방암, 간암세포에서의 항종양 활성이 밝혀져 있으나 난소암에서의 쿠쿠르비타신-I의 역할은 보고된 바 없다. CD44는 세포막에 존재하는 당단백질로 생체 내 리간드인 glycosaminoglycan hyaluronic acid를 통해 세포 외부 매트릭스와 다른 세포와의 접촉을 매개한다. 최근 연구에 의해 CD44의 발현이 난소암세포의 증식 및 세포 부착과 침윤을 증가시키는 주요 원인이라는 것이 보고되었다. 이러한 결과는 CD44의 발현을 억제함으로써 난소암의 진행을 조절할 수 있음을 시사하고 있다. 본 연구에서는 쿠쿠르비타신-I가 난소암세포의 CD44의 발현을 억제할 수 있는 지의 여부를 조사하였다. 인간의 난소암 세포인 SKOV-3를 이용한 MTS assay를 수행한 결과, 쿠쿠르비타신-I는 100 nM이상의 농도에서 세포독성을 나타내었다. 세포독성을 나타내지 않는 농도의 쿠쿠르비타신-I를 SKOV-3 세포에 처리하여 Western blot 분석과 qRT-PCR을 수행한 결과, 쿠쿠르비타신-I에 의해 CD44의 단백질과 mRNA의 발현이 유의적으로 감소되는 것을 확인하였다. 또한 쿠쿠르비타신-I에 의한 CD44의 발현 억제가 $NF-{\kappa}B$와 AP-1의 인산화 감소에 기인하고 있음을 밝혔다. 이러한 결과는 쿠쿠르비타신-I가 CD44 발현을 억제하는 기능을 가지며, 이는 난소암 치료에 도움을 줄 수 있는 제재로서 쿠쿠르비타신-I의 가능성을 제시하는 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1807-1810
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• 2014

Background: It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integral role during intestinal inflammation, an important factor for colon cancer development. Natural compounds from Curcuma longa L. (Zingiberaceae) have long been a potential source of bioactive materials with various beneficial biological functions. Among them, a major active curcuminoid, demethoxycurcumin (DMC) has been shown to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages or microglia cells. However, the role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinal mucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NO production of DMC in inflamed human intestinal Caco-2 cells. An in vitro model was generated and inhibitory effects on NO production of DMC at 65 ${\mu}M$ for 24-96 h were assessed by monitoring nitrite levels. Expression of iNOS mRNA and protein was also investigated. DMC significantly decreased NO secretion by 35-41% in our inflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS at mRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanism of action of DMC may be partly due to its potent inhibition of the iNOS pathway. Our findings suggest that DMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut.

• BMB Reports
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• 제39권6호
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• pp.730-736
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• 2006

To evaluated the effect of recombinant adenovirus Ad-ODC-AdoMetDCas which can simultaneously express both antisense ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) on cell cycle distribution in colorectal cancer cell and investigated underlying regulatory responses, human colorectal cancer cells HT-29 were cultured in RPMI 1640 medium and infected with Ad-ODC-AdoMetDCas. Cell cycle progression was detected by flow cytometry analysis. The expression levels of cell cycle regulated proteins were measured by Western blot analysis. The mRNA level of cyclin D1 was measured by RT-PCR. And a luciferase reporter plasmid of cyclin D1 promoter was constructed to observe the effect of Ad-ODC-AdoMetDCas on cyclin D1 promoter activity. The results showed that recombinant adenovirus Ad-ODC-AdoMetDCas significantly induced $G_1$ arrest, decreased levels of cyclin D1 protein and mRNA and suppressed the promoter activity. Ad-ODC-AdoMetDCas also inhibited nuclear translocation of $\beta$-catenin. In conclusion, downregulation of ODC and AdoMetDC mediated by Ad-ODC-AdoMetDCas transfection induces $G_1$ arrest in HT-29 cells and the arrest was associated with suppression of cyclin D1 expression and inhibition of $\beta$-catenin nuclear translocation. As a new anticancer reagent, the recombinant adenovirus Ad-ODC-AdoMetDCas holds promising hope for the therapy of colorectal cancers.

• 동아시아식생활학회지
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• 제18권3호
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• pp.302-310
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• 2008

In this study, potato kimchi was prepared by applying heat to raw potatoes, and then the physico-chemical properties and anti-cancer effects of the kimchi were analyzed. The texture results indicated the potato kimchi had very good hardness and springiness attributes. During th late storage period, total vitamin C content of the kimchi slowly increased. In addition, the potato kimchi had non-volatile organic acid changes that promoted early aging; however, after the complete aging period, it was comparatively similar to other types of kimchi. Using the methanol extracts of various kimchi samples, the potato kimchi(solid 100%) showed the highest anti-carcinogenic effects in terms of anti-tumor activity in tumor bearing Balb/c mice with sarcoma-180 cells. In addition, the effects of the methanol extracts on hepatic glutathione S-transferase content were $289.76\;{\mu}mol/mg$ protein/min, $250.97\;{\mu}mol/mg$ protein/min, $251.20\;{\mu}mol/mg$ protein/min, $219.53\;{\mu}mol/mg$ protein/min, $183.79\;{\mu}mol/mg$ protein/min, for control kimchi, mul kimchi, and two potato kimchis [(solid 100%) and(solid 60%+kimchi juice 40%)], respectively. The in vivo anti-cancer effects of the potato kimchi were investigated using AGS human gastric adenocarcionoma cells and HT-29 human colon adenocarcionoma cells. Overall, an MTT assay revealed that the methanol extract of the potato kimchi showed the highest anti-carcinogenic effects.

• Journal of Microbiology and Biotechnology
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• 제31권12호
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• pp.1615-1623
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• 2021

Picropodophyllotoxin (PPT), an epimer of podophyllotoxin, is derived from the roots of Podophyllum hexandrum and exerts various biological effects, including anti-proliferation activity. However, the effect of PPT on colorectal cancer cells and the associated cellular mechanisms have not been studied. In the present study, we explored the anticancer activity of PPT and its underlying mechanisms in HCT116 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to monitor cell viability. Flow cytometry was used to evaluate cell cycle distribution, the induction of apoptosis, the level of reactive oxygen species (ROS), assess the mitochondrial membrane potential (Δψm), and multi-caspase activity. Western blot assays were performed to detect the expression of cell cycle regulatory proteins, apoptosis-related proteins, and p38 MAPK (mitogen-activated protein kinase). We found that PPT induced apoptosis, cell cycle arrest at the G1 phase, and ROS in the HCT116 cell line. In addition, PPT enhanced the phosphorylation of p38 MAPK, which regulates apoptosis and PPT-induced apoptosis. The phosphorylation of p38 MAPK was inhibited by an antioxidant agent (N-acetyl-L-cysteine, NAC) and a p38 inhibitor (SB203580). PPT induced depolarization of the mitochondrial inner membrane and caspase-dependent apoptosis, which was attenuated by exposure to Z-VAD-FMK. Overall, these data indicate that PPT induced G1 arrest and apoptosis via ROS generation and activation of the p38 MAPK signaling pathway.

• Journal of Microbiology and Biotechnology
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• 제34권8호
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• pp.1698-1704
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• 2024

Therapeutic advancements in treatments for cancer, a leading cause of mortality worldwide, have lagged behind the increasing incidence of this disease. There is a growing interest in multifaceted approaches for cancer treatment, such as chemotherapy, targeted therapy, and immunotherapy, but due to their low efficacy and severe side effects, there is a need for the development of new cancer therapies. Recently, the human microbiome, which is comprised of various microorganisms, has emerged as an important research field due to its potential impact on cancer treatment. Among these microorganisms, Bifidobacterium infantis has been shown to significantly improve the efficacy of various anticancer drugs. However, research on the role of B. infantis in cancer treatment remains insufficient. Thus, in this study, we explored the anticancer effect of treatment with B. infantis DS1685 supernatant (BI sup) in colorectal and breast cancer cell lines. Treatment with BI sup induced SMAD4 expression to suppress cell growth in colon and breast cancer cells. Furthermore, a decrease in tumor cohesion was observed through the disruption of the regulation of EMT-related genes by BI sup in 3D spheroid models. Based on these findings, we anticipate that BI sup could play an adjunctive role in cancer therapy, and future cotreatment of BI sup with various anticancer drugs may lead to synergistic effects in cancer treatment.