• 동의생리병리학회지
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• 제21권3호
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• pp.721-727
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• 2007

Scorpion (SCP) has been clinically used for the treatment of endogenous wind to relieve convulsion, clearing away toxins, resolving hard masses and removing obstruction in the collaterals to relieve pain. Recent studies showed that scorpion toxins that affect the activating mechanism of sodium channels and indian black scorpion venom induced anti-proliferative and apoptogenic activity against human leukemic cell lines U937 and K562. There is lack of studies regarding the effects of SCP on the immunological activities. The present study was conducted to evaluate the effect of SCP on the regulatory effects of cytokines and nitric oxide (NO) for the immunological activities in Raw 264.7 cells. After the treatment of SCP MeOH extract dissolved in media for 1 h prior to the addition of lipopolysaccharide (LPS: 1 ${\mu}$g/ml), cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. Inducible nitric oxide synthase (iNOS) was determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. As results, SCP inhibited the production of nitrite and nitrate (0.3 and 1.0 mg/ml), iNOS and p-$I_KB_{\alpha}$ protein, tumor necrosis factor-${\alpha}$ (0.3 and 1.0 mg/ml), interleukin-1${\beta}$ (0.3 and 1.0 mg/ml) and interleukin-6 (1.0mg/ml) in Raw 264.7 cells activated with LPS. These findings suggest that SCP can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

• 한국식품위생안전성학회지
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• 제36권1호
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• pp.100-104
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• 2021

트랜스 신남알데하이드(TCA)는 계피의 활성성분 중 하나로 알려져 있으며, 항바이러스, 항균, 항진균 뿐 아니라 일부 암세포주에서 항암 작용이 있다고 보고된 바 있다. 하지만, 위암세포주에서의 보고는 미비하며 그 작용기전에 대해서는 밝혀진 바가 없다. 본 연구에서는 위암 AGS 세포주에 대한 증식 억제작용 및 그 기전을 살펴보았다. TCA는 농도의존적으로 AGS 세포의 생존율을 억제하였다. AGS 세포 형태로 보아 TCA에 의한 세포사멸을 확인할 수 있었다. 그 기전을 확인하기 위하여, 세포사멸 관련 단백질의 발현양을 조사한 결과, TCA는 p53과 Bax의 단백질 발현을 증가시켰다. 또한, 분절된 caspase 9 및 PARP의 발현이 증가되는 것으로부터 TCA가 AGS 세포주의 세포사멸을 유도하였음을 알 수 있었다. 본 연구결과로부터 TCA가 위암에 대한 항암 활성이 있음을 확인하였으며, 추후 지속적인 연구를 통해 항암제 후보물질로 기대된다.

• Nutrition Research and Practice
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• 제17권6호
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• pp.1070-1083
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• 2023

BACKGROUND/OBJECTIVES: Sanghuangporus sanghuang (SS) has various medicinal effects, including anti-inflammation and anticancer activities. Despite the extensive research on SS, its molecular mechanisms of action on lung cancer are unclear. This study examined the impact of an SS alcohol extract (SAE) on lung cancer using in vitro and in vivo models. MATERIALS/METHODS: Different concentrations of SAE were used to culture lung cancer cells (A549 and H1650). A cell counting kit-8 assay was used to detect the survival ability of A549 and H1650 cells. A scratch assay and transwell cell invasion assay were used to detect the migration rate and invasive ability of SAE. Western blot analysis was used to detect the expression of B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), cyclin D1, cyclin-dependent kinases 4 (CDK4), signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3). Lung cancer xenograft mice were used to detect the inhibiting ability of SAE in vivo. Hematoxylin and eosin staining and immunohistochemistry were used to detect the effect of SAE on the structural changes to the tumor and the expression of Bcl-2, Bax, cyclin D1, CDK4, STAT3, and p-STAT3 in lung cancer xenograft mice. RESULTS: SAE could inhibit lung cancer proliferation significantly in vitro and in vivo without cytotoxicity. SAE suppressed the viability, migration, and invasion of lung cancer cells in a dose and time-dependent manner. The SAE treatment significantly decreased the proapoptotic Bcl-2/Bax ratio and the expression of pro-proliferative proteins Cyclin D1 and CDK4 in vitro and in vivo. Furthermore, SAE also inhibited STAT3 expression. CONCLUSIONS: SAE reduced the cell viability and suppressed cell migration and invasion in human lung cancer cells. Moreover, SAE also exhibited anti-proliferation effects in vivo. Therefore, SAE may have benefits in cancer therapy.

• BMB Reports
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• 제39권5호
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• pp.492-501
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• 2006

Since differentiation therapy is one of the promising strategies for treatment of leukemia, universal efforts have been focused on finding new differentiating agents. In that respect, we used guanosine 5'-triphosphate (GTP) to study its effects on K562 cell line. GTP, at concentrations between 25-200 ${\mu}M$, inhibited proliferation (3-90%) and induced 5-78% increase in benzidine-positive cells after 6-days of treatments of K562 cells. Flow cytometric analyses of glycophorine A (GPA) showed that GTP can induce expression of this marker in more mature erythroid cells in a time- and dose-dependent manner. These effects of GTP were also accompanied with inhibition of DNA synthesis (measured by [$^3H$]-thymidine incorporation) and early S-phase cell cycle arrest by 96 h of exposure. In contrast, no detectable effects were observed when GTP administered to unstimulated human peripheral blood lymphocytes (PBL). However, GTP induced an increase in proliferation, DNA synthesis and viability of mitogen-stimulated PBL cells. In addition, growth inhibition and differentiating effects of GTP were also induced by its corresponding nucleotides GDP, GMP and guanosine (Guo). In heat-inactivated medium, where rapid degradation of GTP via extracellular nucleotidases is slow, the anti-proliferative and differentiating effects of all type of guanine nucleotides (except Guo) were significantly decreased. Moreover, adenosine, as an inhibitor of Guo transporter system, markedly reduced the GTP effects in K562 cells, suggesting that the extracellulr degradation of GTP or its final conversion to Guo may account for the mechanism of GTP effects. This view is further supported by the fact that GTP and Guo are both capable of impeding the effects of mycophenolic acid. In conclusion, our data will hopefully have important impact on pharmaceutical evaluation of guanine nucleotides for leukemia treatments.

• IMMUNE NETWORK
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• 제23권6호
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• pp.45.1-45.22
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• 2023

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

• 생명과학회지
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• 제26권7호
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• pp.805-811
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• 2016

본 연구에서는 동충하초 및 부추를 열수추출한 후, 최적배합비율을 선정하여 혼합 물추출물을 제조하고 이에 대한 이화학적 특성 및 생리활성 효능을 검증하고자 하였다. 동충하초 및 부추 혼합 물추출물을 제조하였을 때 소비자들이 가장 선호하는 비율은 70:30이었으며, 이취제거를 위한 첨가물로 10% 사과농축액을 사용하여 최종 혼합 물추출물을 제조하였다. 최적 혼합 물추출물의 이화학적 특성을 확인한 결과로 pH는 4.28±0.12로 약산성이었고, 총 산도는 0.19±0.05%로 나타났다. 당도와 탁도는 9.1°Brix 및 1.48을 나타내었다. 동충하초 및 부추 혼합 물추출물의 항산화능은 DPPH radical 소거능, 환원력 및 ABTS radical 소거능을 통하여 확인하였고, positive control와 유사하거나 다소 낮은 우수한 활성을 나타내었다. 또한, 동충하초 및 부추 혼합 물추출물을 LNCaP 및 RC-58T/h/SA#4 인체 전립선 암세포에 처리한 결과 1% 희석액부터 농도의존적으로 세포성장이 억제되는 경향이 나타났고, 형태학적 관찰에서도 농도의존적으로 세포의 형태학적 변화가 유도되는 것으로 확인되었다. 이상의 결과를 통하여 동충하초 및 부추 혼합 물추출물은 동충하초 단일추출물과 비교하여 항산화 및 암세포 성장 억제효능이 높은 것으로 나타나, 단일 추출물보다는 적합한 비율로 혼합한 추출물이 기능성음료를 제조할 때 높은 활성을 나타낼 것으로 판단된다.

• 생명과학회지
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• 제18권8호
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• pp.1140-1146
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• 2008

본 연구에서는 항균작용, 항암작용, 항산화작용이 있는 것으로 알려져 있는 마늘을 이용하여 소비자의 요구에 부합하는 기능성 전통 고추장 개발을 목표로 마늘죽을 첨가한 고추장을 제조한 후 이에 대한 성분 분석, 항산화능력 및 항암 능력을 살펴본 결과는 다음과 같다. 고추장의 품질 기준으로 평가되는 아미노태 질소함량분석 결과, 마늘죽 첨가 고추장이 시판 고추장에 비해 높은 것으로 나타났으며 숙련된 패널을 대상으로 관능 평가한 결과 생마늘 첨가 고추장이 색을 제외한 항목에 있어 마늘 특유의 향에 대한 거리감으로 인해 낮게 평가된 반면 마늘죽 형태로 첨가한 고추장의 경우 평가항목 모두에서 높은 점수를 얻었다. 질량 분석기를 이용하여 마늘죽 첨가 고추장을 정성 분석한 결과 diallyl disulfide (C6H10S2)와 diallyl trisulfide (C6H10S3)와 같은 유효 기능성 성분인 설파이드계 화합물이 존재하는 곳으로 확인되었다. 항산화 능력은 마늘죽 첨가고추장이 라디칼 소거능 및 환원력에 있어서 모두 시판 고추장에 비해 높은 것으로 조사되었으며 특히 MTT assay법으로 위암(MKN45), 대장암(HCT116), 폐암세포(NCI-H460)를 대상으로 항암효과를 조사한 결과 마늘죽 첨가 고추장의 경우 모든 암세포에 대해 항암효과가 있는 것으로 나타났으며 특히 위암(MKN45)세포에 대한 항암효과가 가장 높은 것으로 나타났다. 결론적으로, 마늘죽 첨가 고추장(마늘 함량 23%, w/w)이 시판 고추장 및 생마늘 첨가 고추장(마늘 함량 10%, w/w)보다 항산화 및 항암효과가 높은 이유는 마늘 함유량이 높기 때문으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6039-6046
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• 2015

Aims: To investigate effect of metallic nanoparticles, silver (AgNPs) and gold nanoparticles (AuNPs) as antitumor treatment in vitro against human breast cancer cells (MCF-7) and their associated mechanisms. This could provide new class of engineered nanoparticles with desired physicochemical properties and may present newer approaches for therapeutic modalities to breast cancer in women. Materials and Methods: A human breast cancer cell line (MCF-7) was used as a model of cells. Metallic nanoparticles were characterized using UV-visible spectra and transmission electron microscopy (TEM). Cytotoxic effects of metallic nanoparticles on MCF-7 cells were followed by colorimetric SRB cell viability assays, microscopy, and cellular uptake. Nature of cell death was further investigated by DNA analysis and flow cytometry. Results: Treatment of MCF-7 with different concentrations of 5-10nm diameter of AgNPs inhibited cell viability in a dose-dependent manner, with IC50 value of $6.28{\mu}M$, whereas treatment of MCF-7 with different concentrations of 13-15nm diameter of AuNPs inhibited cell viability in a dose-dependent manner, with IC50 value of $14.48{\mu}M$. Treatment of cells with a IC50 concentration of AgNPs generated progressive accumulation of cells in the S phase of the cell cycle and prevented entry into the M phase. The treatment of cells with IC50 concentrations of AuNPs similarly generated progressive accumulation of cells in sub-G1 and S phase, and inhibited the entrance of cells into the M phase of the cell cycle. DNA fragmentation, as demonstrated by electrophoresis, indicated induction of apoptosis. Conclusions: Our engineered silver nanoparticles effectively inhibit the proliferation of human breast carcinoma cell line MCF-7 in vitro at high concentration ($1000{\mu}M$) through apoptotic mechanisms, and may be a beneficial agent against human carcinoma but further detailed study is still needed.

• 생명과학회지
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• 제15권3호
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• pp.397-405
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• 2005

브로콜리와 같은 십자화과 식물에서 glucoraphanin의 가수분해를 통해 생성되는 isothiocyanate의 일종인 sulforaphane은 강력한 항암효과를 가지며, 역학적 조사를 포함한 다양한 선행 연구에서 androgen 비 의존적으로 성장하는 전립선 암세포의 증식을 억제하는데 효과가 있었다. 최근 연구 결과에 따르면 sulforaphane은 다양한 인체암세포의 증식을 억제하고 apoptosis를 유발할 수 있는 것으로 알려지고 있으나, 정확한 분자생물학적 기전은 밝혀져 있지 않은 상태이다. 본 연구에서는 sulforaphane의 항암작용 기전을 조사하기 위하여 HeLa 인체자궁경부암세포의 증식에 미치는 sulforaphane의 영향을 조사하였다. Sulforaphane의 처리에 의한 HeLa 세포의 증식억제 및 형태적 변형은 세포주기 C2/M arrest 및 apoptosis 유발과 밀접한 관련이 있음을 알 수 있었다. RT-PCR 및 Western blot 분석 결과, sulforaphane 처리에 의하여 cyclin A 및 cyclin-dependent kinase (Cdk)4 단백질의 발현이 선택적으로 저하되었으며, Cdc2, Cdk inhibitor인 p16 및 p21의 발현은 증가되었다 그러나 sulforaphane은 cyclooxygenases의 발현이나 telomere 조절에 중요한 역할을 하는 인자들의 발현에는 큰 영향을 주지 못하였다. Sulforaphane의 항암 기전을 규명하기 위해서는 더 많은 연구가 부가적으로 필요하겠지만, 본 연구의 결과들에 의하면 sulforaphane은 강력한 인체암세포의 증식 억제 및 항암작용이 있을 것을 시사하여 준다고 할 수 있다.

• 한국수산과학회지
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• 제52권1호
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• pp.35-42
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• 2019

We investigated the protective effects of antioxidant fractions from a 70% ethanolic extract of Hizikia fusiformis in human dermal fibroblasts (HDFs). Powdered H. fusiformis was extracted with 70% ethanol and then partitioned into three fractions according to polarity using n-hexane (HFH), chloroform (HFC), and ethyl acetate (HFEA). Antioxidant activity was observed in HFEA at 0.66 mg/mL based on the half maximal inhibitory concentration ($IC_{50}$) of 1,1-diphenyl-2-picrylhydrazyl (DPPH), and at 0.24 mg/mL based on alkyl radical scavenging. The protective effects of the HFEA antioxidant fraction against 2,2-azobis-(2-amidinopropane) dihydrochloride (AAPH)-damaged HDFs and the expression of Type I procollagen in HDFs were examined. HFEA caused the proliferation of HDFs with and without AAPH treatment and protected against AAPH damage to HDFs in a dose-dependent manner ($50-200{\mu}g/mL$). This implies that the antioxidant properties of the fractions depended on their proliferative and protective effects. The HFEA antioxidant fraction had significant effects and caused the dose-dependent expression of Type I procollagen, an important anti-wrinkle protein, in HDFs. In conclusion, antioxidant substances in H. fusiformis were found in the ethyl acetate fraction, and the resulting HFEA may have cosmetic applications.