• Preventive Nutrition and Food Science
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• 제11권1호
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• pp.1-5
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• 2006

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid that have been used to reduce the incidence, growth and metastasis of breast, colon, prostate and gastric cancer in animals. CLA could reduce tumor growth by altering angiogenesis; a process requiring associated angiogenic factors such as vascular endothelial growth factor (VEGF). In this study, we determined whether CLA could modulate the expression of VEGF in murine mammary tumor cells and adipocytes. The c9, t11-CLA isomer reduced VEGF transcripts and protein when mammary tumor cells were stimulated with PMA. That isomer also reduced VEGF expression in un stimulated mouse 3T3-L1 adipocytes. Since VEGF can be regulated by cyclooxygenase-2 (COX-2), we determined whether CLA could alter COX-2 enzyme expression and $PGE_2$ production. The c9, t11-CLA isomer reduced not only COX-2 enzyme expression but also $PGE_2$ production. Thus, c9, t11-CLA could modulate neovascularization by alteration of VEGF expression from mammary tumor cells and adipocytes by reducing COX-2 metabolites.

• Food Science and Biotechnology
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• 제16권1호
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• pp.167-170
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• 2007

(-)-Epigallocatechin-3-gallate (EGCG), a mai or tea catechin has been shown to have many interesting biological activities. In the present study, we studied the effects of green tea catechins, EGCG metabolites, and black tea theaflavins on accumulation of EGCG in HT-29 human colon cells. Intracellular levels of [$^3H$]-EGCG were not changed significantly in the presence of other tea catechins including (-)-epicatechin, (-)-epigallocatechin, and (-)-epicatechin-3-gallate. EGCG methyl metabolites and EGCG 4"-glucuronide did not affect cellular levels of [$^3H$]-EGCG. Black tea theaflavins and theasinensin A (TsA), an EGCG oxidative dimer, however, significantly decreased cellular accumulation of EGCG in HT-29 cells by 31-56%. This decrease was more pronounced when cells were incubated in the presence of theaflavin-3',3"-digallate (TFdiG) or TsA. When EGCG was added separately from TFdiG or TsA, the accumulation of EGCG in HT-29 cells was also significantly decreased regardless of when TFdiG or TsA was added during the uptake study (p<0.01). The results suggest that theaflavins and TsA may interrupt EGCG absorption through the gastrointestinal epithelium.

• Journal of Microbiology and Biotechnology
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• 제29권4호
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• pp.571-576
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• 2019

Microenvironmental stress, which is naturally observed in solid tumors, has been implicated in anticancer drug resistance. This tumor-specific stress causes the degradation of topoisomerase $II{\alpha}$, rendering cells resistant to topoisomerase $II{\alpha}$-targeted anticancer agents. In addition, microenvironmental stress can induce the overexpression of 78kDa glucose regulated protein (GRP78), which can subsequently block the activation of apoptosis induced by treatment with anticancer agents. Therefore, inhibition of topoisomerase $II{\alpha}$ degradation and reduction in GRP78 expression may be effective strategies for inhibiting anticancer drug resistance. In this study, we investigated the active compound arctigenin, which inhibited microenvironmental stress-induced etoposide resistance in HT-29 cells. Arctigenin was also highly toxic to etoposide-resistant HT-29 cells, with an $IC_{50}$ value of $10{\mu}M$ for colony formation. We further showed that arctigenin inhibited the degradation of topoisomerase $II{\alpha}$ and reduced the expression of GRP78. Thus, these results suggest that arctigenin is a novel therapeutic agent that inhibits resistance to etoposide associated with microenvironmental stress conditions.

• Molecules and Cells
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• 제28권2호
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• pp.99-103
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• 2009

Human endogenous retroviruses (HERVs) have been implicated in the pathogenesis of several human diseases as multi-copy members in the human genome. Their gene expression profiling could provide us with important insights into the pathogenic relationship between HERVs and cancer. In this study, we have evaluated the genomic structure and quantitatively determined the expression patterns in the env gene of a variety of HERV family members located on six specific loci by the RetroTector 10 program, as well as real-time RT-PCR amplification. The env gene transcripts evidenced significant differences in the human tumor/normal adjacent tissues (colon, liver, uterus, lung and testis). As compared to the adjacent normal tissues, high levels of expression were noted in testis tumor tissues for HERV-K, in liver and lung tumor tissues for HERV-R, in liver, lung, and testis tumor tissues for HERV-H, and in colon and liver tumor tissues for HERV-P. These data warrant further studies with larger groups of patients to develop biomarkers for specific human cancers.

• Journal of Microbiology and Biotechnology
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• 제33권9호
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• pp.1206-1212
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• 2023

The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N⁶-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

• 생명과학회지
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• 제17권10호
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• pp.1368-1373
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• 2007

대두를 먼저 헥산(Hex)으로 지방을 제거한 후 메탄올로 추출한 추출물에서 항돌연변이성 및 항암활성 물질을 분리하기 위해 극성이 다른 용매인 디클로로메탄($CH_2Cl_2$), 에틸아세테이트(EtOAC), 부탄올(BuOH)로 분획하여 각 분획물의 항돌연변이 및 항암활성 효과를 검토하였다. $AFB_1$에 대한 돌연변이 억제효과는 대두의 메탄을 추출물(MeOH)의 분획물들 중 디클로로메탄 분획물($CH_2Cl_2$)과 에틸아세테이트 분획물(EtOAc)은 2.5 mg/plate 첨가농도에서 각각 83%로 상당히 높은 항돌연변이 효과를 나타내었다. 중간 분획물(Inter)의 경우는 56%의 항돌연변이 효과를 나타내었으나 다른 분획물들의 경우 항돌연변이 효과가 낮았다. 한편 MNNG의 경우, $AFB_1$에 비해 돌연변이 저해효과가 떨어지지만 그 중에서도 에틸아세테이트 분획물(EtOAc)이 67%로 가장 높은 항돌연변이 효과를 나타내었으며 중간 분획물과 디클로로메탄 분획물($CH_2Cl_2$)은 각각 63%, 49%의 돌연변이 저해효과를 나타내었다. 대두의 메탄을 추출물은 첨가농도 2 mg/assay에서 44%의 인체 위암세포의 증식 억제효과를 가졌고 대두 메탄을 추출물의 분획물들 중 에틸아세테이트층(EtOAC)의 저해 효과가 가장 높았는데 동일농도에서 66%로 위암세포 성장을 저해시키는 효과를 나타내었고 디클로로메탄($CH_2Cl_2$)과 중간 분획물(Inter)의 경우에는 각각 54% 및 51%의 저해효과를 나타내었다. Hep 3B 인체 간암세포의 경우, 대두 메탄을 추출물을 2 mg/assay 투여했을 때 60%의 저해효과를 나타내었으며 여기에서도 분획물들 중에서 에틸아세테이트 분획물(EtOAC)이 73%로 가장 높은 저해효과를 보였다. 대두의 메탄을 추출물은 첨가농도 2 mg/assay에서 44%의 인체 결장암세포 증식억제효과를 가졌고 대두 메탄을 추출물의 분획물들 중 에틸아세테이트층(EtOAC)의 저해 효과가 가장 높았는데 동일농도에서 77%의 결장암세포의 성장을 저해시키는 효과를 나타내었다. 이상의 결과로부터 대두 분획물들 중 특히 에틸아세테이트 분획물에 의한 항돌연변이 및 항암활성효과가 가장 높았으므로 이 분획물에 주로 isofavone류가 함유되어 있으므로 에틸아세테이트 분획물을 더욱 정제하여 연구할 필요가 있다고 여겨진다.

• 한국식품저장유통학회지
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• 제30권2호
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• pp.358-368
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• 2023

본 연구에서는 화살나무 날개를 이용하여 물, 에탄올 및 메탄올을 이용하여 얻은 추출물을 이용하여 항산화 활성, 항당뇨 활성, 총폴리페놀 및 플라보노이드 함량, 암세포 성장 억제능을 평가하였다. 화살나무 날개 추출물은 DPPH radical 소거능 결과에서는 에탄올과 메탄올 추출물에서 positive control과 유사한 radical 소거능을 나타내었으며 ABTS^·+ radical 소거능에서는 모든 군의 1,000 ㎍/mL의 농도에서 80% 이상의 소거능을 보여주었다. 또한, 환원력과 hydrogen peroxide 소거능 및 α-glucosidase 저해활성에서 에탄올과 메탄올 추출물은 positive control과 비슷하거나 높은 활성을 나타내었다. 화살나무 날개 추출물 내 총폴리페놀 및 플라보노이드 함량은 에탄올 추출물에서 867.8 mg% 및 551.7 mg%로 물 및 메탄올 추출물과 비교하였을 때 보다 높은 총폴리페놀 및 플라보노이드 함량이 확인되었다. 화살나무 날개 추출물의 암세포 증식 억제 활성은 흑색종 피부암(B16)에서는 큰 효과를 확인할 수 없었지만 유방암(MDA-MB-231), 대장암(HT-29) 및 전립선암(LNCaP)에서는 유의적인 세포 생존 억제능을 확인하였고 특히 LNCaP에 에탄올 추출물을 처리하였을 때 19.1%의 세포 생존율을 보이며 가장 우수한 세포 성장 억제 활성을 확인하였다. 또한, 전립선 정상 세포인 RWPE-1을 화살나무 날개 추출물로 처리하였을 때 세포 생존율에 큰 영향을 받지 않았기 때문에 암세포 특이적인 성장 억제 활성을 확인할 수 있었다. 이러한 결과를 통해 풍부한 폴리페놀 및 플라보노이드 함량을 가진 화살나무 추출물은 항산화, α- glucosidase 억제, 항암 효과를 나타내어 뛰어난 생리활성효능을 가지고 있고, 이는 효과적인 천연물 유래 기능성 원료 및 식품 소재 발굴을 위한 기초자료로 이용할 수 있을것으로 사료된다.

• Natural Product Sciences
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• 제20권2호
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• pp.130-134
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• 2014

An investigation was carried out to identify novel anti-cancer compounds from Korean indigenous plant extracts. Bioassay-guided fractionation and chemical investigation of the EtOAc extract from the leaves and stems of Stauntonia hexaphylla resulted in the isolation of two active compounds, hederagenin 3-O-${\alpha}$-L-arabinoside (1) and quercetin (2). The structures of these compounds were elucidated by spectroscopic methods, including UV, IR, MS, NMR techniques and compared with previous spectroscopic data. The cytotoxic effects of fractions and compounds on HCT116 human colon cancer cells were evaluated using the MTT assay. Quercetin showed a stronger anti-cancer effect when compared to hederagenin 3-O-${\alpha}$-L-arabinoside.

• Molecules and Cells
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• 제37권12호
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• pp.899-906
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• 2014

Prostaglandin $E_2$ ($PGE_2$) promotes tumor-persistent inflammation, frequently resulting in cancer. Curcumin is a diphenolic turmeric that inhibits carcinogenesis and induces apoptosis. $PGE_2$ inhibits curcumin-induced apoptosis; however, the underlying inhibitory mechanisms in colon cancer cells remain unknown. The aim of the present study is to investigate the survival role of $PGE_2$ and whether addition of exogenous $PGE_2$ affects curcumininduced cell death. HCT-15 cells were treated with curcumin and $PGE_2$, and protein expression levels were investigated via Western blot. Reactive oxygen species (ROS) generation, lipid peroxidation, and intracellular glutathione (GSH) levels were confirmed using specific dyes. The nuclear factor-kappa B ($NF-{\kappa}B$) DNA-binding was measured by electrophoretic mobility shift assay (EMSA). $PGE_2$ inhibited curcumin-induced apoptosis by suppressing oxidative stress and degradation of PARP and lamin B. However, exposure of cells to the EP2 receptor antagonist, AH6809, and the PKA inhibitor, H89, before treatment with $PGE_2$ or curcumin abolished the protective effect of $PGE_2$ and enhanced curcumin-induced cell death. $PGE_2$ activates PKA, which is required for cAMP-mediated transcriptional activation of CREB. $PGE_2$ also activated the Ras/Raf/Erk pathway, and pretreatment with PD98059 abolished the protective effect of $PGE_2$. Furthermore, curcumin treatment greatly reduced phosphorylation of CREB, followed by a concomitant reduction of $NF-{\kappa}B$ (p50 and p65) subunit activation. $PGE_2$ markedly activated nuclear translocation of $NF-{\kappa}B$. EMSA confirmed the DNA-binding activities of $NF-{\kappa}B$ subunits. These results suggest that inhibition of curcumin-induced apoptosis by $PGE_2$ through activation of PKA, Ras, and $NF-{\kappa}B$ signaling pathways may provide a molecular basis for the reversal of curcumin-induced colon carcinoma cell death.

• 생명과학회지
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• 제17권1호
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• pp.110-115
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• 2007

Tumor suppressor 유전자로알려진 early growth response gene 1 (EGR-1)에 있어 항산화 천연물인 apigenin과 그대사물인 isovitexin에 의한 장관 상피성 종양세포에 대하여 항종양 역할을 규명하였다. Apigenin 과 isovitexin은 대장암세포에서의 EGR-1 단백질의 발현을 9-12시간의 노출에 의해 농도 의존적으로 증가하였다. 또한 신호전달측면에서 이런 apigenin에 의한 EGR-1 유전자의 유도가 U0126 화합물에 의해 완벽하게 저해 받는 것으로 보아 ERK1/2 MAP kinase pathway의 이 신호전달계에서의 관여를 보여주었다. 본 연구에서 apigenin에 의해 농도 의존적으로 대장암세포의 세포활성의 저해를 MTT assay를 통해 보였고, 또한 EGR-1 siRNA를 transfectien한 세포의 경우 이런 apigenin에 의한 세포활성의 저해효과를 완화하였다. 따라서 apigenin에 의한 항종암세포 세포활성 억제에 있어 EGR-1의 중요성을 보여 준다. 이런 EGR-1에 의해 유도되는 유전자중 대표적으로 NAG-1 유전자의 경우 apigenin과 isovitexin에 의해 24-48시간에 발현이 증가하였다. 결론적으로 암세포 증식억제활성이 있고 apoptosis 유도효과가 있는 NAG-1의 유도에 의해 대장암 세포의 세포활성이 억제된 것으로 의미되고 향후 apigenin 유도의 NAG-1유전자에 의한 암세포증식의 억제기전에 대한 명확한 연구가 요구된다.