• 대한임상검사과학회지
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• 제51권1호
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• pp.71-77
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• 2019

Menadione은 종양 억제 물질로 알려진 바 있다. 현재 많은 연구에서 다양한 암세포주에 대하여 Menadione의 잠재적인 항암물질로서의 가능성이 보고되었다. 본 연구에서는 Menadione의 항암효과와 세포사멸작용에 연관된 분자신호를 위암세포주에서 확인하였다. Menadione 처리는 위암세포인 MKN45의 세포생존능을 감소시켰다. 감소된 세포생존능은 Western blotting을 통해 caspase-3 과 caspase-7의 활성화와 PARP가 cleavage 된 것을 확인함으로써 세포사멸작용이 유도되었다는 것을 확인했다. 위세포사멸단백질들의 저해제로 작용하는 survivin의 발현을 menadione이 억제한다는 것을 확인함으로써, 세포사멸과정에 포함된 상위조절인자를 확인했다. 우리는 survivin 발현을 조절하는 전사인자로 알려진 ${\beta}$-catenin 또한 menadione에 의해 하향 조절된다는 것을 확인했다. 이전 연구에서 우리는 menadione이 세포사멸유도를 저해는 XIAP의 발현을 억제한다는 것을 확인했으며, menadione이 AGS세포에서 G2/M 세포주기 정체를 유도한다는 것을 확인하였다. 우리는 또 다른 위암세포주인 MKM45 세포에서 menadione의 이전과 다른 항암 기전을 밝혀냈다. 비록 더 자세한 연구가 필요하겠지만, 이 연구를 통해 증명된 억제기전은 menadione에 의한 항암효과를 이해하는 데 도움이 될 것으로 사료된다.

• 한국식품영양과학회지
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• 제39권1호
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• pp.36-41
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• 2010

상황버섯, 영지버섯 및 노루궁뎅이버섯 균사체로 발효된 인삼추출물이 암세포증식에 미치는 영향을 살펴보기 위하여 위암세포(MKN-45), 대장암세포(HCT116), 유방암세포(MCF-7), 폐암세포(NCIH460), 전립선암세포(PC-3) 및 간암세포(HepG2)에 농도별(0.25～1.5 mg/mL)로 처리하여 암세포 성장억제율을 측정하였다. 전립선암 세포에서의 암세포 증식억제 효과는 영지버섯 균사체발효 인삼추출물이 1.5 mg/mL 농도에서 3.07%로 가장 낮은 생존율을 나타내었으며, 상황버섯 균사체발효 인삼추출물이 35.05%, 노루궁뎅이버섯 균사체발효 인삼추출물이 44.29%의 생존율을 보였다. 폐암세포에 대한 세 가지 버섯균사체발효 인삼추출물의 1.5 mg/mL 농도에서 영지버섯 균사체발효 인삼추출물은 5.31%로 우수한 항암활성을 나타낸 반면, 상황버섯 균사체발효 인삼추출물이 53.52%, 노루궁뎅이버섯 균사체발효 인삼추출물이 35.27%의 생존율을 나타내었다. 이러한 결과로부터 영지버섯 균사체로 발효시킨 인삼추출물이 다른 균사체 인삼발효물보다 다양한 암세포에 대한 성장억제 효과가 우수함을 확인할 수 있었다.

• Natural Product Sciences
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• 제19권4호
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• pp.297-302
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• 2013

The current study was conducted to evaluate the antibacterial and antioxidant activities of the essential oil fraction from the roots of Angelica tenuissima Nakai and its main components. We extracted the essential oil fraction from the roots of A. tenuissima using steam distillation and isolated its main components. Their antibacterial activities were determined by broth dilution test against food-borne pathogenic bacteria. Antioxidant activities were evaluated by DPPH-scavenging assay and reducing-power test. Also tested was their ability to inhibit the growth of two gastrointestinal cancer cell lines, Caco-2 and MKN-45. The A. tenuissima oil fraction and its main components, ligustilide and butylidene phthalide exhibited marked inhibitory effects against most of the tested antibiotic-susceptible and antibiotic-resistant bacterial strains with minimum inhibiting concentrations (MICs) from $0.21{\pm}0.08$ to $3.60{\pm}0.89mg/ml$. They also showed growth-inhibiting activity against Caco-2 and MKN-45 cells. The oil fraction showed significant antioxidant activities in DPPH radical scavenging assay and reducing-power test. Taken together, A. tenuissima essential oil could be used as a safe additive for preventing food contamination by pathogenic bacteria. Additionally, its antioxidative activity and the ability to inhibit gastrointestinal carcinoma cell lines could increase its value for functional foods and prevention of cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2839-2843
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• 2013

Objective: To investigate the effects of miR-106b on malignant characteristics of gastric cancer cells, and explore possible mechanisms. Methods: Expression of miR-106b, p21 and E2F was determined by real-time PCR. Transfection with miR-106b mimics was conducted, and gastric cancer cells with miR-106b overexpression were obtained. Cells transfected with mimic mutants and those without transfection served as negative and blank controls, respectively. Flow cytometry and transwell assays were adopted to detect the effects of miR-106b overexpression on cell cycle, migration and invasion of gastric cancer cells. Results:. The expression of miR- 106b in gastric cancer cells was significantly higher than that in normal gastric mucosa cells. Furthermore, the expression level of miR-106b rose according to the degree of malignacy among the three GC cell strains (MKN- 45 > SGC-7901 > MKN-28). Overexpression of miR-106b shortened the G0/G1 phase and accelerated cell cycle progression, while reducing p21 and E2F5, without any significant effects on the capacity for migration and invasion of gastric cancer cells. Conclusions: miR-106b may promote cell cycling of gastric cancer cells through regulation of p21 and E2F5 target gene expression.

• 한국식품영양과학회지
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• 제37권8호
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• pp.1079-1083
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• 2008

본 연구에서는 고추잎 추출물에 대한 항산화 활성과 암세포 증식억제 활성을 분석하고 각 추출물에 따른 차이를 비교 분석하고자 하였다. 추출물의 항산화력은 ABTS와 DPPH 라디칼 제거능, 환원력 및 금속이온 제거능을 이용하여 평가하였으며 암세포 증식 억제능은 유방암, 대장암 및 위암 세포주를 이용하였다. 각 추출물 중 70% acetone 추출물의 경우 polyphenol 함량(56.6 mg GAE/g residue)과 총 항산화력(450.8 mM TEAC/g residue), DPPH 라디칼 제거능(230.3 mM TEAC/g residue), 환원력(0.5 A700) 측정에서 모두 가장 높은 수치를 나타내었다. 또한 암세포 증식억제활성 측정 결과 대장암세포(HCT116)에서는 70% acetone 추출물이 1 mg/mL의 농도에서 96.2%의 증식억제 활성을 나타냈고 유방암세포(MCF7)에서는 methanol 추출물이 78.4%의 활성을 나타냈으며, 위암세포(MKN45)에서는 water 추출물이 89.7%의 활성을 나타내었다. 본 연구결과는 점차 관심이 높아지고 있는 천연 항산화 항암제로서의 고추잎에 대한 활성연구에 있어 기초자료가 될 것으로 예상되며, 주산물인 고추열매에 비해 그 활용도가 극히 적은 고추잎에 대한 소비촉진에 영향을 끼칠 것으로 기대된다.

• Journal of Gastric Cancer
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• 제11권1호
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• pp.16-22
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• 2011

Purpose: Eupatilin is an antioxidative flavone and a phytopharmaceutical derived from Artemisia asiatica. It has been reported to possess anti-tumor activity in some types of cancer including gastric cancer. Eupatilin may modulate the angiogenesis pathway which is part of anti-inflammatory effect demonstrated in gastric mucosal injury models. Here we investigated the anti-tumor effects of eupatilin on gastric cancer cells and elucidated the potential underlying mechanism whereby eupatilin suppresses angiogenesis and tumor growth. Materials and Methods: The impact of eupatilin on the expression of angiogenesis pathway proteins was assessed using western blots in MKN45 cells. Using a chromatin immunoprecipitation assay, we tested whether eupatilin affects the recruitment of signal transducer and activator of transcription 3 (STAT3), aryl hydrocarbon receptor nuclear translocator (ARNT) and hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) to the human VEGF promoter. To investigate the effect of eupatilin on vasculogenesis, tube formation assays were conducted using human umbilical vein endothelial cells (HUVECs). The effect of eupatilin on tumor suppression in mouse xenografts was assessed. Results: Eupatilin significantly reduced VEGF, ARNT and STAT3 expression prominently under hypoxic conditions. The recruitment of STAT3, ARNT and HIF-$1{\alpha}$ to the VEGF promoter was inhibited by eupatilin treatment. HUVECs produced much foreshortened and severely broken tubes with eupatilin treatment. In addition, eupatilin effectively reduced tumor growth in a mouse xenograft model. Conclusions: Our results indicate that eupatilin inhibits angiogenesis in gastric cancer cells by blocking STAT3 and VEGF expression, suggesting its therapeutic potential in the treatment of gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.201-208
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• 2013

Objective: To investigate changes in the invasive capacity of gastric cancer cells in vitro after expression inhibition of T lymphoma invasion and metastasis inducing factor 1 (Tiam 1) and underlying mechanisms. Methods: Using adhesion selection, two subpopulations with high ($M_H$) or low ($M_L$) invasive capacity were separated from the human gastric cancer cell line MKN-45 ($M_0$). Tiam 1 antisense oligodeoxynucleotide (ASODN) was transfected into $M_H$ cells with liposomes, and expression of Tiam 1 mRNA and protein was determined by RT-PCR and quantitative cellular-ELISA. Changes in the cytoskeleton, invasive capacity in vitro and expression of ras-related $C_3$ botulinum toxin substrate 1 (Rac 1), integrin ${\beta}1$ and matrix metalloproteinase 2 (MMP 2) between Tiam 1 ASODN transfected $M_H$ cells and non-transfected cells were observed by HE staining, cytoskeletal protein staining, scanning electron microscopy, Boyden chamber tests and cyto-immunohistochemistry. Results: A positive correlation existed between the expression level of Tiam l mRNA or protein and the invasion capacity of gastric cancer cells. After ASODN treatment ($0.43{\mu}M$ for 48 h), Tiam 1 mRNA transcription and protein expression in $M_H$ cells were decreased by 80% and 24% respectively (P < 0.05), compared with untreated controls, while invasive capacity in vitro was suppressed by 60% (P < 0.05). Morphologic and ultrastructural observation also showed that ASODN-treated $M_H$ cells exhibited smooth surfaces with obviously reduced filopodia and microspikes, which resembled $M_0$ and $M_L$ cells. Additionally, cytoskeletal distribution dramatically altered from disorder to regularity with reduced long filament-like structure, projections, pseudopodia on cell surface, and with decreased acitn-bodies in cytoplasm. After Tiam 1 ASODN treatment, the expression of Rac 1 and Integrin ${\beta}1$ in $M_H$ cells was not affected (P > 0.05), but that of MMP 2 in $M_H$ cells was significantly inhibited compared with untreated cells (P < 0.05). Conclusion: Over-expression of Tiam-1 contributes to the invasive phenotype of gastric cancer cells. Inhibition of Tiam 1 expression could impair the invasive capacity of gastric cancer cells through modulating reconstruction of the cytoskeleton and regulating expression of MMP 2.

• 한국축산식품학회지
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• 제22권1호
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• pp.72-76
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• 2002

상업적으로 생산 판매되고 있는 여러 가지 유청 단백질을 이용하여 각종 암세포에 대한 세포독성을 조사한 결과, IgG, BSA, $\beta$-LG는 세포독성이 거의 없었으나, $\alpha$-LA가 강한 세포독성을 갖고 있음이 확인되었다. MKN45, HeLa, WiDr, 그리고 A498의 경우, $\alpha$-LA(1mg/ml)에 의해 세포성장이 95% 이상 억제되는 것으로 나타났다. HPLC를 이용하여 $\alpha$-LA에 혼입되어 있는 미량성분을 제거한 후, 세포독성을 조사한 결과, $\alpha$-LA이 나타내었던 세포독성이 대부분 없어지는 것으로 나타났다. 또한 $\alpha$-LA을 trypsin으로 부분 가수분해한 후, 각종 암세포에 대한 성장 억제효과를 검토한 결과, 암세포에 대한 독성을 상실하는 것으로 나타났으며, $\alpha$-LA를 EDTA로 처리할 경우, $\alpha$-LA의 세포독성이 대부분 상실되는 것으로 나타났다.

• 한국식품영양학회지
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• 제25권3호
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• pp.447-453
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• 2012

Various types of tea are consumed as a popular beverage worldwide particularly in Asian countries such as Korea, China, and Japan. The purpose of this study was to investigate the mineral contents, antioxidant properties and anticancer activity of Yak-Sun tea that is prepared by six oriental medicinal herbs. The results of the mineral contents were as follows; Ca, Mg, and Na contents were higher than those of green tea, whereas Fe, P, and K contents were lower than those of green tea. The total phenolics and flavonoid content of the Yak-Sun tea were higher than those of green and black teas. The $IC_{50}$ values of DPPH radical, hydroxyl radical, hydrogen peroxide radical scavenging of Yak-Sun tea were 0.78, 1.58, and 2.04 $mg/m{\ell}$, respectively, whereas the radical scavenging values of ${\alpha}$-tocopherol was 0.06, 0.05, and 0.09 $mg/m{\ell}$, respectively. When cancer cells were treated with Yak-Sun tea, the anticancer activity increased in a dose dependent manner. HCT116 colon cancer cell lines were dramatically increased, as compared to other cancer cell lines, such as MCF-7, H460, and MKN45 cell lines. The results of this study demonstrated that Yak-Sun tea could function as a tea to enhance health conditions for antioxidant and anticancer activity.

• Molecules and Cells
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• 제41권5호
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• pp.390-400
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• 2018

Studies have revealed that miR-103a-3p contributes to tumor growth in several human cancers, and high miR-103a-3p expression is associated with poor prognosis in advanced gastric cancer (GC) patients. Moreover, bioinformatics analysis has shown that miR-103a-3p is upregulated in The Cancer Genome Atlas (TCGA) stomach cancer cohort. These results suggest that miR-103a-3p may function as an oncogene in GC. The present study aimed to investigate the role of miR-103a-3p in human GC. miR-103a-3p expression levels were increased in 33 clinical GC specimens compared with adjacent nontumor stomach tissues. Gain- and loss-of-function studies were performed to identify the correlation between miR-103a-3p and tumorigenesis in human GC. Inhibiting miR-103a-3p suppressed GC cell proliferation and blocked the S-G2/M transition in MKN-45/SGC-7901 cells, whereas miR-103a-3p overexpression improved GC cell proliferation and promoted the S-G2/M transition in vitro. Bioinformatics and dual-luciferase reporter assays confirmed that ATF7 is a direct target of miR-103a-3p. Analysis of the TCGA stomach cancer cohort further revealed that miR-103a-3p expression was inversely correlated with ATF7 expression. Notably, silencing ATF7 showed similar cellular and molecular effects as miR-103a-3p overexpression, namely, increased GC cell proliferation, improved CDK2 expression and decreased P27 expression. ATF7 overexpression eliminated the effects of miR-103a-3p expression. These findings indicate that miR-103a-3p promotes the proliferation of GC cell by targeting and suppressing ATF7 in vitro.