• 제목/요약/키워드: reactive oxygen species

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목근피(木槿皮)가 CT105와 ${\beta}A$로 유도된 Alzheimer's Disease 병태(病態) 모델에 미치는 영향 (The Effects of Hibiscus syriacus(HSS) Extract on the Alzheimer's Disease Model Induced by CT-105 and ${\beta}A$)

  • 최병만;정인철;이상룡
    • 동의신경정신과학회지
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    • 제15권2호
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    • pp.119-139
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    • 2004
  • This research investigates the effect of the Hibiscus syriacus(HSS) on Alzheimer's disease. Specifically, the effects of the HSS extract on (1) $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ mRNA of PC-12 cells treated with LPS; (2) amyloid precursor proteins(APP), acetylcholinesterase(AChE), and glial fibrillary acidic protein(GFAP) mRNA of PC-12 cells treated with CT-105; (3) the AChE activity and the APP production of PC-12 cell treated with CT-105; (4) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, $IL-1{\beta}$ mRNA, $TNF-{\alpha}$ mRNA, and reactive oxygen species(ROS); (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. The results were summarized below ; 1. The HSS extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in THP-l cells treated with LPS. 2. The HSS extract suppressed the expression of APP, AChE, and GFAP mRNA in PC-12 cells treated with CT-105. 3. The HSS extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 4. For the HSS extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 5. The HSS extract suppressed the over-expression of $IL-1{\beta}$, $TNF-{\alpha}$, $IL-1{\beta}$ and $TNF-{\alpha}$ mRNA, CD68/GFAP, ROS in the mice with Alzheimer's disease induced by ${\beta}A$. 6. The HSS extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. These results suggest that the HSS extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the HSS extract for Alzheimer's disease is suggested for future research.

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백수오(白首烏)의 항산화 효능 및 모유두 세포의 5α-reductase mRNA 발현 억제 효능 (Investigation of Antioxidant Activity of Cynanchi Wilfordii Radix and Inhibitory Effect of 5α-reductase mRNA in Human Dermal Papilla Cells)

  • 조남준;최영호;전해리;이웅희;김기광;한효상
    • 동의생리병리학회지
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    • 제31권6호
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    • pp.374-379
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    • 2017
  • Hair loss affects interpersonal relationships and causes psychological stress. In this study, we investigated the antioxidant activity of Cynanchi Wilfordii Radix (CWR) and its effects on dermal papilla (DP) cells. Antioxidant efficacy was examined by ABTS assay. To confirm the effect on cell activity, MTS assay was performed and cell count was directly measured by hemocytometer. The mRNA expression of genes involved in hair formation and hair loss formation was confirmed by quantitative RT-PCR. CWR has a strong antioxidant activity. Cell viability of DP cells was increased to 118.5% by treatment of 0.5 mg/ml CWR for 24 hours, but the effect on the cell number was insignificant. These results suggest that CWR increases mitochondrial activity without promoting cell proliferation. Treatment of DP cells with 0.5 mg/ml CWR resulted in 48.5% reduction of mRNA expression of type 2 $5{\alpha}$-reductase, a major cause of male hair loss. In addition, mRNA expression of bone morphogenetic pretein (BMP), fibroblast growth factor (FGF)7, and FGF10, which are closely related to hair growth, was also decreased. Reactive oxygen species (ROS) acts as a cause of hair loss. The excellent antioxidant efficacy of CWR is thought to be able to effectively remove ROS. The dihydrotestosterone produced by type 2 $5{\alpha}$-reductase in DP cells is a potent inducer of male pattern hair loss. The inhibitory effect of type 2 $5{\alpha}$-reductase mRNA on DP cells induced by CWR may induce a positive therapeutic effect of male pattern hair loss.

간세포에서 PAH의 구조 의존적 작용기전 (Structure-dependent Mechanism of Action of Poly Aromatic Hydrocarbons in Cultured Primary Hepatocytes)

  • 김선영;홍성범;양재호
    • Toxicological Research
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    • 제22권1호
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    • pp.23-30
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    • 2006
  • Among poly aromatic hydrocarbons, dioxin and PCBs are the most controversial environmental pollutants in our modern life. These pollutants are known as human carcinogens, and liver is the most sensitive target in animal cancer models. Specific aims of the study were focused on the mechanism of carcinogenesis in hepatocytes and the structure-activity relation among these diverse environmental chemicals. Because key mechanisms of dioxin-induced carcinogenesis in human epithelial cell model are the alteration of signal transduction pathway and PKC isoforms, the alteration of the signal transduction pathways and other factors associated with carcinogenesis were studied. Rat hepatocytes cultured under the sandwich protocols were exposed with the various concentration of dioxins and PCBs, and signal transduction pathway, protein kinase C isoforms, oxidant stress, and apoptotic nuclei were evaluated. Since it is important to understand the structure-activity relation among these chemicals to properly assess the carcinogenic potentials, the study analyzed the parameters associated with carcinogenic processes, based on their structural characteristics. In addition, signal transduction pathways and PKC isoforms involved in inhibition of UV-induced apoptosis were also analyzed to elaborate the tumor promotion mechanism of these chemicals. Induction of apoptosis by UV irradiation was optimal at $60\;J/m^2$ in primary hepatocyte in culture. Compared to non coplanar PCBs such as PCB 114 and PCB 153, coplanar PCBs such as PCB 77 and PCB126 showed a stronger inhibition of apoptosis induced by UV irradiation. Production of reactive oxygen species (ROS) was more stimulated by non-coplanar PCBs than coplanar PCBs with the most potent induction of ROS by chlorinated non-coplanar PCB. As compared to the level of induction by PCB126, non-coplanar PCB153 showed a higher increase of intracellular concentrations. Besides the alteration of intracellular calcium concentration, translocation of PKC from cytosolic fraction to membrane fraction was clearly observed upon the exposure of non-coplanar PCB. Taken together, the present study demonstrated that there is a potent structure-activity relationship among PCB congeners and the mechanism of PAH-induced carcinogenesis is structure-specific. The study suggested that more diverse pathways of PAH-induced carcinogenesis should be taken into account beyond the boundary of Ah receptor dogma to assess the health impact of PAH with more accuracy.

PEMOCVD of Ti(C,N) Thin Films on D2 Steel and Si(100) Substrates at Low Growth Temperatures

  • Kim, Myung-Chan;Heo, Cheol-Ho;Boo, Jin-Hyo;Cho,Yong-Ki;Han, Jeon-Geon
    • 한국진공학회:학술대회논문집
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    • 한국진공학회 1999년도 제17회 학술발표회 논문개요집
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    • pp.211-211
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    • 1999
  • Titanium nitride (TiN) thin films have useful properties including high hardness, good electrical conductivity, high melting point, and chemical inertness. The applications have included wear-resistant hard coatings on machine tools and bearings, decorative coating making use of the golden color, thermal control coatings for widows, and erosion resistant coatings for spacecraft plasma probes. For all these applications as feature sizes shrink and aspect ratios grow, the issue of good step coverage becomes increasingly important. It is therefore essential to manufacture conformal coatings of TiN. The growth of TiN thin films by chemical vapor deposition (CVD) is of great interest for achieving conformal deposition. The most widely used precursor for TiN is TiCl4 and NH3. However, chlorine impurity in the as-grown films and relatively high deposition temperature (>$600^{\circ}C$) are considered major drawbacks from actual device fabrication. To overcome these problems, recently, MOCVD processes including plasma assisted have been suggested. In this study, therefore, we have doposited Ti(C, N) thin films on Si(100) and D2 steel substrates in the temperature range of 150-30$0^{\circ}C$ using tetrakis diethylamido titanium (TDEAT) and titanium isopropoxide (TIP) by pulsed DC plamsa enhanced metal-organic chemical vapor deposition (PEMOCVD) method. Polycrystalline Ti(C, N) thin films were successfully grown on either D2 steel or Si(100) surfaces at temperature as low as 15$0^{\circ}C$. Compositions of the as-grown films were determined with XPS and RBS. From XPS analysis, thin films of Ti(C, N) with low oxygen concentration were obtained. RBS data were also confirmed the changes of stoichiometry and microhardness of our films. Radical formation and ionization behaviors in plasma are analyzed by optical emission spectroscopy (OES) at various pulsed bias and gases conditions. H2 and He+H2 gases are used as carrier gases to compare plasma parameter and the effect of N2 and NH3 gases as reactive gas is also evaluated in reduction of C content of the films. In this study, we fond that He and H2 mixture gas is very effective in enhancing ionization of radicals, especially N resulting is high hardness. The higher hardness of film is obtained to be ca. 1700 HK 0.01 but it depends on gas species and bias voltage. The proper process is evident for H and N2 gas atmosphere and bias voltage of 600V. However, NH3 gas highly reduces formation of CN radical, thereby decreasing C content of Ti(C, N) thin films in a great deal. Compared to PVD TiN films, the Ti(C, N) film grown by PEMOCVD has very good conformability; the step coverage exceeds 85% with an aspect ratio of more than 3.

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참산부추(Allium sacculiferum Max.) 메탄올 추출물의 지방세포 내 ROS 생성 및 지질 축적 억제 효능 (Inhibitory Effects of Allium sacculiferum Max. Methanol Extracts on ROS Production and Lipid Accumulation during Differentiation of 3T3-L1 Cells)

  • 최혜영;김건희
    • 한국식품영양과학회지
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    • 제43권6호
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    • pp.822-828
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    • 2014
  • 본 연구에서는 3T3-L1 지방전구세포를 이용하여 Allium 속 식물의 하나인 참산부추(ASM) 메탄올 추출물의 ROS 생성 저해 및 지질 축적 억제 효과를 확인하고자 하였다. 먼저 ASM 메탄올 추출물 $100{\sim}2,000{\mu}g/mL$의 모든 농도에서 유의적인 DPPH 라디칼 소거능을 나타내었으며, 지방전구세포에 ASM 메탄올 추출물 $10{\sim}100{\mu}g/mL$를 처리하였을 때 세포 독성을 나타내지 않았다. 지방세포 내 ROS 관련 효소와 분화 관련 전사인자의 조절로 인한 중성지방 축적 저해 활성을 확인하기 위하여 지방전구세포를 분화 유도하면서 추출물을 농도별(10, 50, $100{\mu}g/mL$)로 처리하였다. 그 결과 ASM 메탄올 추출물은 대조군에 비해 ROS 생성량과 ROS 관련 효소인 G6PDH mRNA 발현을 농도 의존적으로 감소시켰다. 또한 ASM 메탄올 추출물에 의하여 지방세포 내 중성지방 축적량이 유의적으로 감소하였으며, 지방세포 분화에 관련된 전사인자인 SREBP1c, $PPAR{\gamma}$$C/EBP{\alpha}$ mRNA 발현도 유의적으로 감소하였다. 이상의 결과들로 볼 때 ASM 메탄올 추출물로 인한 ROS 생성 저해와 지질 축적 억제는 ROS 생성 및 ROS 관련 유전자의 발현감소로 인한 지방 생성 주요 전사인자의 유전자 발현 억제로 인한 것으로 보이며, ASM이 항비만 효과가 있는 천연물 소재로 개발 가능성이 있을 것으로 사료된다.

Seminal Plasma Heparin Binding Proteins Improve Semen Quality by Reducing Oxidative Stress during Cryopreservation of Cattle Bull Semen

  • Patel, Maulikkumar;Gandotra, Vinod K.;Cheema, Ranjna S.;Bansal, Amrit K.;Kumar, Ajeet
    • Asian-Australasian Journal of Animal Sciences
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    • 제29권9호
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    • pp.1247-1255
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    • 2016
  • Heparin binding proteins (HBPs) are produced by accessory glands. These are secreted into the seminal fluid, bind to the spermatozoa at the time of ejaculation, favour capacitation, acrosome reaction, and alter the immune system response toward the sperm. The present study was conducted with an objective to assess the effect of purified seminal plasma-HBPs (SP-HBPs) on cross bred cattle bull sperm attributes during two phases of cryopreservation: Pre freezing and freezing-thawing. SP-HBPs were purified from pooled seminal plasma by heparin affinity chromatography. Three doses of SP-HBPs i.e. 10, 20, $40{\mu}g/mLs$ semen were standardized to find out the optimum dose and $20{\mu}g/mLs$ was found to be an optimum dose. Semen as such and treated with SP-HBPs was diluted with sodium citrate-egg yolk diluter and cryopreserved as per the standard protocol. Sperm parameters i.e. motility, viability, Hypo-osmotic swelling test (HOST), acrosome damage, in vitro capacitation and lipid peroxidation were evaluated in SP-HBP treated and untreated (control) semen at both phases of cryopreservation. A considerable variation in percent sperm motility, viability, membrane integrity (HOST), acrosome damage, acrosome reaction and lipid peroxidation was observed at both phases among the bulls irrespective of the treatment. Incubation of neat semen with $20{\mu}g/mL$ SP-HBP before processing for cryopreservation enhanced the average motility, viability, membrane integrity by 7.2%, 1.5%, 7.9%, and 5.6%, 6.6%, 7.4% in pre-frozen and frozen-thawed semen in comparison to control. There was also an average increase of 4.1%/3.9% in in vitro capacitation and acrosome reaction in SP-HBPs-treated frozen-thawed semen as compared to control. However, binding of SP-HBPs to the sperm declined acrosome damage and lipid peroxidation by 1.3%/4.1% and 22.1/$32.7{\mu}M$/$10^9$ spermatozoa in SP-HBP treated pre-frozen/frozen-thawed semen as compared to control, respectively. Significant (p<0.05) effects were observed only in motility, HOST and in vitro acrosome reaction. It can be concluded that treatment of neat semen with SP-HBPs before cryopreservation minimized the cryoinjury by decreasing the generation of reactive oxygen species.

Serum 8 Hydroxydeoxyguanosine and Cytotoxin Associated Gene A as Markers for Helicobacter pylori Infection

  • Yeniova, Abdullah Ozgur;Uzman, Metin;Kefeli, Ayse;Basyigit, Sebahat;Ata, Naim;Dal, Kursat;Guresci, Servet;Nazligul, Yasar
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권13호
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    • pp.5199-5203
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    • 2015
  • Background: Helicobacter pylori (H.pylori) is associated with chronic gastritis, peptic ulcers, gastric adenocarcinomas and mucosa associated tissue lymphomas. Cytotoxin associated gene A (CagA) is one of the virulence factors of H.pylori. It is hypothesized that reactive oxygen species (ROS) play roles in H.pylori associated disease especially in development of gastric adenocarcinoma. Individuals infected with H.pylori bearing CagA produce more ROS than others. 8-hydroxydeoxyguanosine (8OHdG) is an in vitro marker of DNA damage and oxidative stress. The aim of this study was to investigate the relationship between 8OHdG level, H.pylori infection and CagA and alterations of serum 8OHdG level after H.pylori eradication. Materials and Methods: Patients admitted with dyspeptic complaints and upper gastrointestinal endoscopy were assessed. H.pylori was determined from histopathology of specimens. Serum 8OHdG levels of three groups (H.pylori negative, H. pylori positive CagA negative and H.pylori positive CagA positive) were compared. Patients with H.pylori infection received eradication therapy. Serum 8OHdG levels pretreatment and posttreatment were also compared. Results: In total, 129 patients (M/F, 57/72) were enrolled in the study. Serum 8OHdG level of H.pylori negative, H. pylori positive CagA negative and H.pylori positive CagA positive groups were significantly different ($5.77{\pm}1.35ng/ml$, $5.43{\pm}1.14ng/ml$ and $7.57{\pm}1.25ng/ml$ respectively, p=0.05). Furthermore, eradication therapy reduced serum 8OHdG level ($6.10{\pm}1.54ng/ml$ vs $5.55{\pm}1.23ng/ml$, p=0.05). Conclusions: Individuals infected with H.pylori bearing CagA strains have the highest serum 8OHdG level and eradication therapy decreases the serum 8OHdG level. To the best of our knowledge this is the first study that evaluated the effect of CagA virulence factor on serum 8OHdG level and the effect of eradication therapy on serum 8OHdG levels together. Eradication of CagA bearing H.pylori may prevent gastric adenocarcinoma by decreasing ROS. 8OHdG level may thus be a good marker for prevention from gastric adenocarcinoma.

PC12 신경세포주에서 녹각영지버섯 주정 추출물의 산화 스트레스 개선 효과 (Protective effect of ethanolic extract of antler-shaped Ganoderma lingzhi against oxidative stress in PC12 neuronal cell line)

  • 김형돈;이은영;박정용;서경혜;이강효;최재훈;한재구;조재한;이승은
    • 한국버섯학회지
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    • 제16권3호
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    • pp.213-217
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    • 2018
  • 알츠하이머병, 파킨슨병 등 신경퇴행성질환은 ROS 축적에 의한 산화 스트레스가 주된 원인 중 하나인 것으로 알려져 있다. 따라서 본 연구에서는 신경세포 내 ROS 생성을 억제하는 약용 버섯 추출물을 탐색하여, 녹각영지버섯 추출물을 선발하였다. 실험 결과, PC12 신경세포에서 $H_2O_2$ $50{\mu}M$ 처리에 의해 증가한 ROS 생성이 녹각영지버섯 추출물에 의해 억제되었다. 녹각영지버섯 추출물은 우수한 ABTS 라디칼 소거능($IC_{50}:46.90{\mu}g/ml$)을 가지고 있었으며, 신경세포에서 산화자극에 의한 ROS 생성을 농도의존적으로 억제하였다. 이러한 녹각영지버섯 추출물의 ROS 생성 억제능은 형광현미경 관찰을 통해서도 확인하였다. 본 연구의 실험 결과들은 녹각영지버섯의 항치매 기능성 소재로서의 가치를 보여주는 결과라고 할 수 있다.

H2O2 Inhibits Proliferation and Mediates Suppression of Migration via DLC1/RhoA Signaling in Cancer Cells

  • Ma, Long;Zhu, Wen-Zhen;Liu, Ting-Ting;Fu, Hui-Ling;Liu, Zhao-Jun;Yang, Bing-Wu;Song, Tai-Yu;Li, Guo-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권4호
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    • pp.1637-1642
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    • 2015
  • Background: RhoGTPase-activating proteins (RhoGAPs) regulate RhoGTPases in cells, but whether individual reactive oxygen species (ROS) regulate RhoGAPs is unknown. Our previous published papers have shown that deleted in liver cancer 1 (DLC1) inhibits cancer cell migration by its RhoGAP activity. The present study was designed to explore the role of $H_2O_2$ in regulation of DLC1. Materials and Methods: We treated cells with $H_2O_2$ for 24h and phenotypic changes were analyzed by MTT, RT-PCR, Western blotting, immunofluorescence staining and wound healing assays. Results: $H_2O_2$ downregulated cyclin D1 and cyclin E to inhibit proliferation, and upregulated BAX to induce apoptosis in MCF-7 cells. Compared with non-tumorigenic cells, $H_2O_2$ increased expression of DLC1 and reduced activity of RhoA in cancer cells. Stress fiber production and migration were also suppressed by $H_2O_2$ in MDA-MB-231 cells. Conclusions: Our study suggests that $H_2O_2$ inhibits proliferation through modulation of cell cycle and apoptosis-related genes, and inhibits migration by decreasing stress fibers via DLC1/RhoA signaling.

2-deoxy-D-Glucose Synergizes with Doxorubicin or L-Buthionine Sulfoximine to Reduce Adhesion and Migration of Breast Cancer Cells

  • Mustafa, Ebtihal H;Mahmoud, Huda T;Al-Hudhud, Mariam Y;Abdalla, Maher Y;Ahmad, Iman M;Yasin, Salem R;Elkarmi, Ali Z;Tahtamouni, Lubna H
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권8호
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    • pp.3213-3222
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    • 2015
  • Background: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. Materials and Methods: T47D human breast cancer cells were treated with 2-deoxy-D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent-phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. Results: Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. Conclusions: Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.