• Title/Summary/Keyword: 세포독성 치료

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Effect of Anti-oxidant, Anti-inflammatory and Anti-invasive of PMA-induced Matrix Metalloproteinase (MMP-2) and MMP-9 Activities of Water Extract and Solvent Fractions of Saururus Chinensis (삼백초 물 추출물과 유기용매 분획물의 항산화, 항염증 및 PMA에 의해 유도된 MMP-2 및 MMP-9활성 침윤 억제 효과)

  • Kim, Jun-Ho;Kim, Eun-Jung
    • Journal of Life Science
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    • v.26 no.5
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    • pp.584-591
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    • 2016
  • Saururus chinensis is a perennial plants, its flavonoid compound is known to exhibit anti-oxidative activity. This study was aimed to investigate the effect of Water Extract and Solvent Fractions of Saururus chinensis on antioxidant, anti-inflammatory and anti-invasive of Phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP-2) and MMP-9 activities. Plant samples were fractionated into hexane, CHCl3, ethyl acetate, butanol, and water fractions, and each of these was assayed individually. The water fraction showed the highest extraction yield at 9.25%(w/w). Anti-oxidative activity was analyzed by DPPH assay. Cell viability was detected by the MTS assay. Anti-inflammatory activity was assayed by the nitric oxide (NO) production in mouse macrophage Raw 264.7 cells. The activity and mRNA expression of MMP-2 and MMP-9 in human oral squamous carcinoma YD-10B cells were examined by zymography and RT-PCR. As results, MMP-2/-9 activation was increased in PMA induced YD-10B cells. In PMA-treated YD-10B cells, the increased mRNA expression and protein activation of MMP-2/-9 were significantly inhibited in the ethyl acetate fraction. The ethyl acetate fraction showed the highest anti-oxidative activity at 73.38%. The ethyl acetate fraction at non-cytotoxic concentrations significantly exhibited the anti-inflammatory activity of Raw 264.7 cells in dose-dependent manner. In conclusion, these findings demonstrate that the ethyl acetate fraction obtained from a chinensis water extract potentiates a promising therapeutic anti-invasive agent and, therefore, as an anti-cancer drug for cancer prevention and therapy in oral cancer.

The Anti-cancer Effects of Bigihwan, Daechilgithang, and Mokwhyangbinranghwan Ethanol Extracts in Human Hepatocellular Carcinoma Cells (인체 간암세포에서 비기환(肥氣丸), 대칠기탕(大七氣湯) 및 목향빈랑환(木香檳榔丸)의 항암 활성 비교)

  • Kim, So Young;Hong, Su Hyun;Choi, Sung Hyun;Cheong, JaeHun;Choi, Yung Hyun
    • Journal of Life Science
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    • v.30 no.5
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    • pp.460-467
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    • 2020
  • Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers in the word. Although radiation and chemotherapy are generally effective, there are various side effects that greatly limit the effectiveness of these treatments. Therefore, traditional herbs may have potential as important resources for the discovery of liver cancer therapeutics. In this study, we selected three Korean herbal medicine formulas from the Donguibogam, namely Bigihwan (BGH), Daechilgithang (DCGT), and Mokwhyangbinranghwan (MHBRH), and evaluated their anti-cancer effects on HCC cells. According to our results of three ethanol extracts, BGH was more effective at suppressing HCC growth than DCGT or MHBRH. Furthermore, flow cytometry analysis showed that inhibition of HCC proliferation by the three extracts was associated with the induction of apoptosis and autophagy. In particular, BGH significantly increased mitochondrial impairment and showed the possibility of inducing mitophagy in comparison with the other two extracts. BGH prominently upregulated the levels of microtubule-associated protein light chain-3 which was accompanied by a decrease in the expression of anti-apoptotic Bcl-2 without altering the expression of pro-apoptotic Bax. In addition, the levels of PTEN-induced kinase 1 were also markedly increased in BGH-treated HCC cells. Moreover, autophagy blocking improved cell viability and reduced apoptosis after the three treatments, indicating that autophagy by these extracts enhances HCC cells against cytotoxicity. In conclusion, our findings show that BGH demonstrates the highest anti-cancer activity among the three formulas and inhibits the proliferation of HCC cells through autophagy induction.

Bacterial Toxin-antitoxin Systems and Their Biotechnological Applications (박테리아의 toxin-antitoxin system과 생명공학기술 응용)

  • Kim, Yoonji;Hwang, Jihwan
    • Journal of Life Science
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    • v.26 no.2
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    • pp.265-274
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    • 2016
  • Toxin-antitoxin (TA) systems are ubiquitous genetic modules that are evolutionally conserved in bacteria and archaea. TA systems composed of an intracellular toxin and its antidote (antitoxin) are currently classified into five types. Commonly, activation of toxins under stress conditions inhibits diverse cellular processes and consequently induces cell death or reversible growth inhibition. These effects of toxins play various physiological roles in such as regulation of gene expression, growth control (stress response), programmed cell arrest, persister cells, programmed cell death, phage protection, stabilization of mobile genetic elements or postsegregational killing of plasmid-free cells. Accordingly, bacterial TA systems are commonly considered as stress-responsive genetic modules. However, molecule screening for activation of toxin in TA system is available as development of antimicrobial agents. In addition, cytotoxic effect induced by toxin is used as effective cloning method with antitoxic effect of antitoxin; consequently cells containing cloning vector inserted a target gene can survive and false-positive transformants are removed. Also, TA system is applicable to efficient single protein production in biotechnology industry because toxins that are site-specific ribonuclease inhibit protein synthesis except for target protein. Furthermore, some TA systems that induce apoptosis in eukaryotic cells such as cancer cells or virus-infected cells would have a wide range of applications in eukaryotes, and it will lead to new ways of treating human disease. In this review, we summarize the current knowledge on bacterial TA systems and their applications.

A Study on the Whitening Effects of Pueraria thomsonii Extract and its Three Tectorigenin Derivatives (분갈화 추출물과 분갈화 유래 Tectorigenin류 3종의 미백 효능에 대한 연구)

  • Ahn, Young Je;Chang, Yun Hee;Lee, So Young;Jin, Mu Hyun
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.45 no.1
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    • pp.49-56
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    • 2019
  • Pueraria thomsonii Benth. as a medicinal ingredient, has been traditionally used in Chinese medicine to treat fever, acute dysentery, diarrhea, diabetes, and cardiovascular disease. The effects of P. thomsonii flower on skin have not been reported yet. In this study, the whitening effect of P. thomsonii flower was verified using B16F1 melanoma cells and HS68 fibroblasts. P. thomsonii flower extract reduced melanin contents of B16F1 cells in a dose-dependent manner. To identify its active components, we analyzed P. thomsonii flower extract using high performance liquid chromatography (HPLC). As a result, we identified three major isoflavones of tectorigenin, tectoridin, and tectorigenin 7-O-xylosylglucoside. At a non-cytotoxic concentration, the three components also reduced melanin contents of B16F1 cells in a dose-dependent manner. The depigmentation effects were attributed to the reduced gene expression of tyrosinase and microphthalmia-associated transcription factor (MITF). In order to elucidate another depigmentation mechanism, their effects on DKK-1, a fibroblast-derived depigmentation factor, was determined in HS68 cells. As a result, P. thomsonii flower extracts, tectoridin and tectorigenin 7-O-xylosylglucoside, reduced DKK-1 gene expression, while tectorigenin increased DKK-1 gene expression in a dose-dependent manner. These results suggest that tectorigenin can be used as an effective whitening agent that inhibit melanin synthesis in melanocytes and promote the secretion of depigmentation factor from fibroblasts.

The Inhibitory Effect of Nicotine on TNF-α Expression in Human Fetal Astrocytes (담배 니코틴에 의한 사람 태아 성상세포에서 종양괴사인자(TNF-α)의 발현 억제작용)

  • Son, Il-Hong;Lee, Sung-Ik;Yang, Hyun-Duk;Han, Sun-Jung;Suk, Seung-Han;Lee, Jai-Kyoo;Kim, Jae-Hyun;Park, Joo-Young;Moon, Hyung-In;Lee, Sung-Soo
    • Journal of the Korean Chemical Society
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    • v.51 no.3
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    • pp.251-257
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    • 2007
  • The Tumor necrosis factor-α, (TNF-α), is involved in the pathogenesis of multiple sclerosis and contributes to the degeneration of oligodendrocytes as well as neurons. Nicotine has been found to have immunosuppressive and inflammation-suppressing effects. Astrocytes, the major glial cells in the CNS, are capable of producing TNF-α at both the mRNA and protein levels in response to interleukin-1 (IL-1) or TNF-α. Nicotine has been shown to influence glial cell functions. To order to explore the role of astrocytes in the production of TNF-α, astrocytes were pretreated with nicotine and are stimulated with IL-1β to determine their effects on TNF-α production. The results are as follows. Cytotoxic effects of nicotine on human fetal astrocytes were noted above 10 μg/ml of nicotine. The effect of IL-1β on TNF-α mRNA expression in primary cultured human fetal astrocytes was maximal at 2 h after IL- 1β(100 pg/ml) treatment. Human fetal astrocytes were pretreated with 0.1, 1, and 10 μg/ml of nicotine and then stimulated with IL-1β (100 pg/ml) for 2 h. The inhibitory effect of nicotine on expressions of TNF-α mRNA in human fetal astrocytes with pretreated 0.1 μg/ml of nicotine is first noted at 8 hr, and the inhibitory effect is maximal at 12 h. The inhibitory effect at 1 μg/ml of nicotine is inhibited maximal at 24 h. Nicotine at 0.1, 1 and 10 μg/ml concentrations significantly inhibits IL-1β-induced NF-κB activation. Collectively, this study indicates that nicotine might inhibit the expression of TNF-α in activated human fetal astrocytes.

Protective effect of lycopene against cytokine-induced β-cell apoptosis in INS-1 cells (라이코펜이 사이토카인에 의해 유도된 베타세포 사멸에 미치는 효과 및 기전 연구)

  • Kim, Kyong;Jang, Se-Eun;Bae, Gong Deuk;Jun, Hee-Sook;Oh, Yoon Sin
    • Journal of Nutrition and Health
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    • v.51 no.6
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    • pp.498-506
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    • 2018
  • Purpose: Lycopene, a carotenoid with anti-oxidant properties, occurs naturally in tomatoes and pink grapefruit. Although the beneficial effects of lycopene on various disorders have been established, little attention has been paid to the possible anti-diabetic effects of lycopene focusing on ${\beta}$-cells. Therefore, this study investigated the potential of lycopene to protect ${\beta}$-cells against apoptosis induced by a cytokine mixture. Methods: For toxicity experiments, the cells were treated with 0.1 ~ 10 nM of lycopene, and the cell viability in INS-1 cells (a rat ${\beta}$-cell line) was measured using a MTT assay. To induce cytokine toxicity, the cells were treated with a cytokine mixture (20 ng/mL of $TNF{\alpha}$ + 20 ng/mL of IL-$1{\beta}$) for 24 h, and the effects of lycopene (0.1 nM) on the cytokine toxicity were measured using the MTT assay. The expression levels of the apoptotic proteins were analyzed by Western blotting, and the level of intracellular reactive oxidative stress (ROS) was monitored using a DCFDA fluorescent probe. The intracellular ATP levels were determined using a luminescence kit, and mRNA expression of the genes coding for anti-oxidative stress response and mitochondrial function were analyzed by quantitative reverse-transcriptase PCR. Results: Exposure of INS-1 cells to 0.1 nM of lycopene increased the cell viability significantly, and protected the cells from cytokine-induced death. Lycopene upregulated the mRNA and protein expression of B-cell lymphoma-2 (Bcl-2) and reduced the expression of the Bcl-2 associated X (Bax) protein. Lycopene inhibited apoptotic signaling via a reduction of the ROS, and this effect correlated with the upregulation of anti-oxidative stress response genes, such as GCLC, NQO1, and HO-1. Lycopene increased the mRNA expression of mitochondrial function-related genes and increased the cellular ATP level. Conclusion: These results suggest that lycopene reduces the level of oxidative stress and improves the mitochondrial function, contributing to the prevention of cytokine-induced ${\beta}$-cell apoptosis. Therefore, lycopene could potentially serve as a preventive and therapeutic agent for the treatment of type 2 diabetes.

Wound Healing Effect of Curcumin Gel for Transdermal Delivery (경피전달을 위한 커큐민 젤의 창상치유효과)

  • Kim, Jin;Kim, Man Jong;Lee, Ki-Young
    • Polymer(Korea)
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    • v.37 no.3
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    • pp.387-392
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    • 2013
  • The aim of this study was to investigate the effect of trasdermal delivery of the curcumin gel on healing of the rats' dorsum wounds. Carbopol 934 and propylene glycol were used to prepare gels containing 1% curcumin. Curcumin gel was evaluated for various properties such as antioxidant, cell viability, anti-inflammatory, in vivo wound healing. The free radical scavenging activity using 1,1-diphenyl-2-picryl hydrazyl (DPPH) was 50% at 12.5 ppm concentration. Inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells by curcumin gel. In the curcumin gel-treated group, the re-epithelialization in wounds was significantly increased compared to the control group throughout the experimental period. These results suggested that curcumin may be helpful for the promotion of wound healing.

The Effects of Herbal Extract Mixture on Anti-Obesity (항비만에 대한 생약복합물의 효과)

  • Chin, Hwi-Seung;Pack, Keum-Ju;Pack, Seung-Hee;Kim, Jae-Ki
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.1
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    • pp.32-38
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    • 2009
  • In this study, we investigated the anti-obesity activity of the herbal extract mixture (HEM). The inhibitory effect of HEM on triglyceride accumulation of 3T3-L1 preadipocyte was examined by Oil-Red O staining. HEM inhibited the triglyceride accumulation of 3T3-L1 preadipocyte cell and reduced glycerol-3-phosphate dehydrogenase (GPDH) activity. We further investigated the effect of HEM in prevention of obesity in male ICR mouse for 5 weeks. Experimental groups were divided into high fat diet group (HFD), HFD supplemented with 100 mg/kg HEM group (HEM1) and HFD supplemented with 200 mg/kg HEM group (HEM2). Body weight and food efficiency ration of HEM1 and HEM2 was decreased by 52% and 50% and by 45% and 50%, respectively. The amount of adipocyte in body weight was decreased. Blood triglyceride and total cholesterol of HEM1 was significantly decreased. These results indicate that HEM may be useful in preventing obesity.

Effect of Increased Intracellular pH by HMA on the Cytotoxicity of Combined Treatment of Hyperthermia and Chemotherapy (HMA의 세포내 산도증가가 온열과 항암화학 치료의 세포독성에 미치는 효과)

  • Hur, Won-Joo;Song, Chang-Won
    • Radiation Oncology Journal
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    • v.13 no.2
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    • pp.121-128
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    • 1995
  • Purpose: The enhanced cytotoxic effect of combined treatment of hyper-thermia and chemotherapy by increasing intracellular acidity with HMA was investigated. Materials and Methods: FSall tumor cells were injected on the hindlegs of female $C_3H$ mice. When the tumor volume reached about 200mm3, experiments were performed on the groups classified as follows: Group I :Control, Group II : Melphalan alone (2.5mg/kg, 5mg/kg, 10mg/kg, 15mg/kg), Group III : Heat alone $(42.5^{\cdot}C$ for 1 hour) Group IV : Melphalan + Heat $(42.5^{\cdot}C$ for 1 hour), Group V : HMA(10mg/kg) + Melphalan(5.0mg/kg) + Heat$(42.5^{\cdot}C$ for 1hour). Each group included 8-12 mice on each experiment HMA (3-amino-6-chloro-5-(1-homopiperidyl )-N-(diaminomethylene) -c-pyrazinecarboxamide), an analog of amiloride which increases intracellular pH(pHi) was dissolved in dimethyl sulfoxide (DMS) and injected into the tumor-bearing mice through the tail vein. 10mg/kg of HMA and each dose of melphalan were injected into peritoneum of the tumor-bearing mice 30 minutes before heating. Tumor growth delay was calculated when the tumor volme reached at $1500mm^3$ Excision assay was performed on each group and repeated 2-4 times. Results : Tumor growth delay of each experimental groups at $1500mm^3$ were 9, 10, 13 and 19 days respectively. In vivo-in vitro excision assay using FSall tumor cells, the cytotoxicity of each experimental groups was $1.2{\times}10^7,\;1{\times}10^7,\;6{\times}10^6,\;1.7{\times}10^6\;and\;1{\times}10^5$ clonogenic cells/gm respectively When HMA was added to the combined treatment of heat and .chemotherapy, the tumor growth was delayed more than combined treatment without HMA i.e., 6 days tumor growth delay at $1500mm^3$ of tumor volume. Conclusion: The combined effect of cytotoxicity by heat and chemotherapy can be much more enhanced by HMA.

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Effect of Brussels Sprouts Extract on Inflammatory Cytokine Inhibition (방울양배추 추출물의 염증성 사이토카인 억제에 미치는 영향)

  • Jae-Hyeok Lee;Jeong-Sook Park
    • Journal of Industrial Convergence
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    • v.21 no.8
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    • pp.69-74
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    • 2023
  • This paper was conducted to examine the effect of Brussels Sprouts Extract on the inhibition of pro-inflammatory cytokines. The inflammatory response is manifested by mediators such as reactive oxygen species and inflammatory cytokines such as TNF-α, IL-1β, and IL-8. Therefore, this paper examined the toxicity to cells using the MTS assay, stimulated RAW264.7 macrophages with lipopolysaccharide (LPS), and stimulated reactive oxygen species such as NO and TNF-α, IL-1β, and IL-8. Inhibition of inflammatory cytokines after treatment with 10 mg/mL, 100 mg/mL, and 1000 mg/mL of Brussels Sprouts Extract was investigated. As a result of the experiment, Brussels Sprouts Extract inhibited NO production, TNF-α and IL-8 in a concentration-dependent manner without cytotoxicity, and showed significant inhibition especially at a concentration of 1000 mg/mL. Brussels Sprouts Extract, which inhibits the production of inflammatory cytokines, suggests the possibility of reducing inflammatory response and controlling inflammation, and can be seen as providing potential as a health functional food or prevention and treatment of inflammation.