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ABSTRACT: The intestine-specific transcription factor, caudal type homeobox-1 (CDX1), is a candidate tumor suppressor gene that plays key roles in regulating intestinal epithelial differentiation and proliferation. It is aberrantly down-regulated in colorectal cancers and colon cancer-derived cell lines by promoter hypermethylation. Since the effects of oxidative stress on the transcription of tumor suppressor genes are largely unknown, this study explored the epigenetic alterations that occur during reactive oxygen species (ROS)-induced silencing of CDX1 in colorectal cancer cells. Oxidative stress by hydrogen peroxide (H2O2) down-regulated CDX1 mRNA levels and protein expression in the human colorectal cancer cell line, T-84. This down-regulation was abolished by pretreatment with the ROS scavenger, N-acetylcysteine. In addition, the DNA methylation inhibitor, 5-aza-2-deoxycytidine (5-Aza-dC) markedly attenuated the decrease in mRNA and protein expression levels induced by H2O2. Moreover, methylation-specific PCR data revealed that H2O2 treatment increased CDX1 promoter methylation, and treatment with 5-Aza-dC reversed this effect, suggesting that an epigenetic regulatory mechanism triggered by ROS-induced methylation may be involved in CDX1 expression. Furthermore, H2O2 treatment resulted in up-regulation of DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1) expression and activity, and enhanced the association between DNMT1 and HDAC1. Taken together, these results suggest that ROS-induced oxidative stress silences the tumor suppressor CDX1 through epigenetic regulation, and may therefore be associated with the progression of colorectal cancer.
Gene 04/2013; · 2.34 Impact Factor
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ABSTRACT: This study focused on the protective actions of against ultraviolet B (UVB) radiation in human HaCaT keratinocytes. An ethyl acetate extract of (ENE) increased cell viability decreased by exposure to UVB rays. ENE also absorbed UVB radiation and scavenged UVB-induced intracellular reactive oxygen species (ROS) in HaCaT keratinocytes. In addition, ENE shielded HaCaT keratinocytes from damage to cellular components (e.g., peroxidation of lipids, modification of proteins, and breakage of DNA strands) following UVB irradiation. Furthermore, ENE protected against UVB-induced apoptotic cell death, as determined by a reduction in the numbers of apoptotic bodies and sub-G hypodiploid cells, as well as by the recovery of mitochondrial membrane potential. The results of the current study therefore suggest that ENE safeguards human keratinocytes against UVB-induced cellular damage via the absorption of UVB ray and scavenging of UVB-generated ROS.
Evidence-based Complementary and Alternative Medicine 01/2013; 2013:983609. · 4.77 Impact Factor
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ABSTRACT: Ultraviolet B generates reactive oxygen species by interacting with water in irradiated skin tissues and cells in turn causes lipid peroxidation, protein modification and further DNA damage.
This study examined the cytoprotective effects of phloroglucinol (1,3,5-trihydroxybenzene) on ultraviolet B-irradiated cultured human keratinocytes.
The human keratinocyte cell line HaCaT cells were treated with 10 μM of phloroglucinol. After 1 h, the cells were irradiated with ultraviolet B light at 30 mJ/cm(2) and incubated at 37°C.
Phloroglucinol scavenged both the superoxide anion and hydroxyl radical in a cell-free system and ultraviolet B-induced intracellular reactive oxygen species. Phloroglucinol reduced ultraviolet B-generated lipid peroxidation, protein modification and DNA strand breaks. The enzymatic effects of phloroglucinol restored cellular glutathione levels, superoxide dismutase and catalase activities, which were impaired by ultraviolet B radiation.
Phloroglucinol provides the protective effects in human keratinocyte cell line exposed to ultraviolet B radiation, suggesting that phloroglucinol can be used as a photoprotective agent.
Photodermatology Photoimmunology and Photomedicine 12/2012; 28(6):322-31. · 1.30 Impact Factor
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ABSTRACT: Oxidative stress caused by reactive oxygen species (ROS) induces DNA base modifications and DNA strand breaks. In this study, the protective effect of baicalein against H(2)O(2)-induced DNA damage was investigated in V79-4 Chinese hamster fibroblast cells. H(2)O(2) treatment increased the levels of intracellular ROS and DNA double-strand breaks (DSBs) and decreased the level of Ku70 protein and the phosphorylation (activation) of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which are involved in the repair of DSBs by nonhomologous end joining. Baicalein effectively scavenged intracellular ROS induced by H(2)O(2), reduced DSBs, and rescued Ku70 protein level and phosphorylation of DNA-PKcs. In cellular response to DNA base damage, 8-oxoguanine DNA glycosylase 1 (OGG1) plays a vital role in the removal of 8-oxoguanine (8-OxoG), which is formed mainly by oxidative stress. Baicalein significantly decreased the levels of 8-OxoG induced by H(2)O(2), and this correlated with increases in OGG1 promoter activity and OGG1 mRNA and protein expression. The phosphorylated form of Akt kinase, which is a regulator of OGG1, was sharply decreased by H(2)O(2), but was prevented by baicalein. A specific Akt inhibitor abolished the cytoprotective effects of baicalein, suggesting that OGG1 induction by baicalein involves the Akt pathway. In conclusion, baicalein exerted protective effects against DNA damage induced by oxidative stress by activating DNA repair systems and scavenging ROS.
Cell Biology and Toxicology 09/2012; · 2.51 Impact Factor
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ABSTRACT: KIOM-4 is a plant extract obtained from Magnolia officinalis, Pueraria lobata, Glycyrrhiza uralensis, and Euphorbia pekinensis. Previously, we reported that KIOM-4 protects pancreatic β-cells against streptozotocin (STZ) induced oxidative stress. To
elucidate the cytoprotective mechanism of KIOM-4 on oxidative stress, we focused on the induction of heme oxygenase-1 (HO-1),
which plays a role in cytoprotection against oxidative injury as well as providing an important function in the maintenance
of homeostasis, in rat pancreatic β-cells (RINm5F). In this study, we showed that KIOM-4 up-regulated HO-1 expression at the
mRNA and protein levels, thus resulting in increased HO-1 activity. HO-1 induction is regulated at the transcriptional level
and is mediated by a specific enhancer, the antioxidant response element (ARE), which is found in the promoter of HO-1 gene.
The transcription factor, NF-E2 related factor 2 (Nrf2), interacts with the ARE to activate HO-1 gene transcription and results
in the modulation of HO-1 expression. KIOM-4 increased the nuclear translocation, ARE binding, and transcriptional activity
of Nrf2. In addition, the extracellular regulated kinase (ERK) positively contributed to ARE-driven HO-1 expression. Furthermore,
KIOM-4 elicited the activation of ERK and U0126 (inhibitor of ERK) attenuated the KIOM-4 induced activation of Nrf2, which
subsequently decreased HO-1 protein levels. These findings suggest that the induction of HO-1 by KIOM-4 is dependent on the
ERK pathway. Taken together, KIOM-4 enhances the cellular antioxidant defense system through the induction of HO-1 via the ERK-Nrf2-ARE signaling pathway, thereby protecting cells from streptozotocin-induced cell damage.
Biotechnology and Bioprocess Engineering 04/2012; 14(3):295-301. · 1.28 Impact Factor
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Kyoung Ah Kang,
Young Hee Maeng,
Rui Zhang,
Young Ro Yang,
Mei Jing Piao, Ki Cheon Kim,
Gi Young Kim,
Young Ree Kim,
Young Sang Koh,
Hee Kyoung Kang,
Chang Lim Hyun,
Weon Young Chang,
Jin Won Hyun
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ABSTRACT: Heme oxygenase-1 (HO-1) catabolizes heme into carbon monoxide, biliverdin, and free iron which mediate its protective effect against oxidative stress. The aim of the present study was to determine the expression level and activity of HO-1 in Korean colon cancer tissues and cell lines. HO-1 protein expression was higher (>1.5-fold) in tumor tissues than in adjacent normal tissues in 14 of 20 colon cancer patients, and HO-1 protein expression was closely correlated with HO-1 enzyme activity in cancer tissues. Immunohistochemical data confirmed that HO-1 protein was expressed at a higher level in colon cancer tissues than in normal mucosa. Furthermore, HO-1 mRNA and protein expression and enzyme activity were higher in the colon cancer cell lines Caco-2, SNU-407, SNU-1033, HT-29, and SW-403 than in the normal fetal human colon cell line FHC. Treatment with the HO-1 inhibitor zinc protoporphyrin decreased the viability of colon cancer cell lines. These data indicate that HO-1 may serve as a clinically useful biomarker of colon cancer and as a target for anticolon cancer drugs.
Tumor Biology 02/2012; 33(4):1031-8. · 1.94 Impact Factor
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ABSTRACT: Oxidative stress is related to the synthesis of matrix metalloproteinases (MMPs), which cause skin aging. The protective effects of mangiferin derived from Anemarrhena asphodeloides were investigated against hydrogen peroxide (H(2)O(2))-induced damage using human skin keratinocyte (HaCaT) cells. Mangiferin was found to scavenge intracellular reactive oxygen species (ROS), superoxide radicals, and hydroxyl radicals. ROS regulate MMPs gene expression and activation of proenzymes. Mangiferin inhibited H(2)O(2)-induced MMP-1 gene expression and protein levels as well as its activity. Moreover, it abrogated mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway and stress-activated protein kinase/extracellular signal-regulated kinase (SEK)-c-JUN N-terminal kinase (JNK) pathway, which are induced by H(2)O(2) treatment. And, it inhibited DNA binding activity of activator protein-1 (AP-1), a transcription factor of MMP-1 and downstream of ERK and JNK. Finally, it protected the human skin keratinocytes from H(2)O(2)-induced cell death. Taken together, these results indicate that mangiferin attenuated H(2)O(2)-induced MMP-1 activation via inhibition of ERK and JNK pathway and AP-1.
Bioscience Biotechnology and Biochemistry 12/2011; 75(12):2321-5. · 1.28 Impact Factor
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ABSTRACT: Although silver nanoparticles (AgNPs) have been reported to exert strong acute toxic effects on various cultured cells by inducing oxidative stress, the molecular mechanisms by which AgNPs-damaged cells are unknown. Because the endoplasmic reticulum (ER) may play an important role in the response to oxidative stress-induced damage and is quite sensitive to oxidative damage, we hypothesized that AgNPs may exert cytotoxic effects on cells by modulating ER stress. In our study, AgNPs resulted in cytotoxicity and apoptotic cell death when analyzing cell viability, DNA fragmentation and the apoptotic sub-G(1) population. Flow cytometry and confocal microscopy indicated that the cells were sensitive to AgNPs with respect to the induction of mitochondrial Ca(2+) overloading and enhancement of ER stress. AgNPs induced a number of signature ER stress markers, including phosphorylation of RNA-dependent protein kinase-like ER kinase (PERK) and its downstream eukaryotic initiation factor 2α, phosphorylation of inositol-requiring protein 1 (IRE1), splicing of ER stress-specific X-box transcription factor-1, cleavage of activating transcription factor 6 (ATF6) and up-regulation of glucose-regulated protein-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP/GADD153). Down-regulation of PERK, IRE1 and ATF6 expression using siRNA significantly decreased AgNPs-induced the enhancement of ER stress. In addition, down-regulation of CHOP expression with siRNA CHOP attenuated AgNPs-induced apoptosis. Taken together, the present study supports an important role for the ER stress response in mediating AgNPs-induced apoptosis.
The international journal of biochemistry & cell biology 11/2011; 44(1):224-32. · 4.89 Impact Factor
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ABSTRACT: Recently, we reported that silver nanoparticles (AgNPs) induced reactive oxygen species (ROS) generation and the resultant oxidative stress contributes to the cell damage associated with AgNPs. 8-Oxoguanine (8-oxoG) is sensitive marker of ROS-induced DNA damage. 8-Oxoguanine DNA glycosylase 1 (OGG1) is an important DNA repair enzyme that recognizes and excises 8-oxoG. The aim of the present study was to examine the effect of AgNPs-induced oxidative stress on OGG1 and to elucidate mechanisms underlying AgNPs toxicity. AgNPs decreased OGG1 mRNA and protein expression, resulting in decreased OGG1 activity. Decreased OGG1 activity in AgNPs-treated cells led to increased 8-oxoG levels. The transcription factor NF-E2-related factor 2 (Nrf2) is an important factor in the inducible regulation of OGG1. AgNPs treatment decreased nuclear Nrf2 expression, translocation into nucleus, and transcriptional activity of Nrf2. Extracellular regulated kinase (ERK) and protein kinase B (PKB, AKT), which are upstream of Nrf2, contribute to OGG1 expression. AgNPs attenuated both active forms of ERK and AKT protein expression, resulting in suppression of Nrf2 and decrease of OGG1 expression. These studies demonstrate that down-regulation of Nrf2-mediated OGG1 in exposure to AgNPs occurs through ERK and AKT inactivation.
Toxicology Letters 09/2011; 207(2):143-8. · 3.23 Impact Factor
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ABSTRACT: The radioprotective effect of geraniin, a tannin compound isolated from Nymphaea tetragona Georgi var. (Nymphaeaceae), against γ-radiation-induced damage was investigated in Chinese hamster lung fibroblast (V79-4) cells. Geraniin recovered cell viability detected by MTT test and colony formation assay, which was compromised by γ-radiation, and reduced the γ-radiation-induced apoptosis by the inhibition of loss of the mitochondrial membrane potential. Geraniin protected cellular components (lipid membrane, cellular protein, and DNA) damaged by γ-radiation, which was detected by lipid peroxidation, protein carbonyl formation, and comet assay. Geraniin significantly reduced the level of intracellular reactive oxygen species generated by γ-radiation, which was detected using spectrofluorometer, flow cytometer, and confocal microscope after 2',7'-dichlorodihydrofluorescein diacetate staining. Geraniin normalized the superoxide dismutase and catalase activities, which were decreased by γ-radiation. These results suggest that geraniin protects cells against radiation-induced oxidative stress via enhancing of antioxidant enzyme activities and attenuating of cellular damage.
Cell Biology and Toxicology 04/2011; 27(2):83-94. · 2.51 Impact Factor
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ABSTRACT: Formaldehyde (HCHO) generates reactive oxygen species (ROS) that induce DNA base modifications and DNA strand breaks and contributes to mutagenesis and other pathological processes. DNA non-homologous end-joining (NHEJ), a major mechanism for repairing DNA double-stranded breaks (DSB) in mammalian cells, involves the formation of a Ku protein heterodimer and recruitment of a DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to the site of DNA damage. HCHO treatment induced DSB and decreased the protein expressions of Ku 70 and phosphorylated DNA-PKcs. Triphlorethol-A reduced DNA strand breaks and restored the expression of NHEJ-related proteins. In response to oxidative DNA base damage, 8-oxoguanine DNA glycosylase 1 (OGG1) plays a vital role in repair of 8-hydroxy-2'-deoxyguanosine (8-OhdG) via the base-excision repair (BER) process. In this study, HCHO significantly increased 8-OhdG levels, whereas triphlorethol-A lowered 8-OhdG levels. Suppression of 8-OhdG formation by triphlorethol-A was related to enhanced OGG1 protein expression. Triphlorethol-A also enhanced the expression of phosphorylated Akt (the active form of Akt), a regulator of OGG1, which was found to be decreased by HCHO treatment. The phosphoinositol 3-kinase (PI3K)-specific inhibitor LY294002 abolished the cytoprotective effects induced by triphlorethol-A, suggesting that OGG1 restoration by triphlorethol-A is involved in the PI3K/Akt pathway. These results suggest that triphlorethol-A may protect cells against HCHO-induced DNA damage via enhancement of NHEJ and BER capacity.
Journal of Toxicology and Environmental Health Part A 01/2011; 74(12):811-21. · 1.83 Impact Factor
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Nguyen Xuan Nhiem, Ki Cheon Kim,
Areum-Daseul Kim,
Jin Won Hyun,
Hee Kyoung Kang,
Phan Van Kiem,
Chau Van Minh,
Vu Kim Thu,
Bui Huu Tai,
Jeong Ah Kim,
Young Ho Kim
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ABSTRACT: By various chromatographic methods, one new phenylpropanoid, acanthopanic acid (1), and three known compounds, 1,2-O-dicaffeoylcyclopenta-3-ol (2), (4S)-α-terpineol 8-O-β-D-glucopyranoside (3), and rutin (4), were isolated from the methanol extract of the Acanthopanax koreanum leaves. Their structures were elucidated on the basis of spectroscopic analyses, and their antioxidant activities were evaluated by the intracellular reactive oxygen species (ROS) radical scavenging 2',7'-dichlorofluorescein diacetate assay. Among them, compounds 1, 2, and 4 showed significant scavenging capacity with IC(50) values of 3.8, 2.6, and 2.9 μM, respectively, and compound 3 showed weak scavenging capacity with the inhibition rate of 37% at 40 μM.
Journal of Asian natural products research 01/2011; 13(1):56-61. · 0.61 Impact Factor
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ABSTRACT: Recently, we demonstrated that butin (7,3',4'-trihydroxydihydroflavone) protected cells against hydrogen peroxide (H(2)O(2))-induced apoptosis by: (1) scavenging reactive oxygen species (ROS), activating antioxidant enzymes such superoxide dismutase and catalase; (2) decreasing oxidative stress-induced 8-hydroxy-2'-deoxyguanosine levels via activation of oxoguanine glycosylase 1, and (3), reducing oxidative stress-induced mitochondrial dysfunction. The objective of this study was to determine the cytoprotective effects of butin on oxidative stress-induced mitochondria-dependent apoptosis, and possible mechanisms involved. Butin significantly reduced H(2)O(2)-induced loss of mitochondrial membrane potential as determined by confocal image analysis and flow cytometry, alterations in Bcl-2 family proteins such as decrease in Bcl-2 expression and increase in Bax and phospho Bcl-2 expression, release of cytochrome c from mitochondria into the cytosol and activation of caspases 9 and 3. Furthermore, the anti-apoptotic effect of butin was exerted via inhibition of mitogen-activated protein kinase kinase-4, c-Jun NH(2)-terminal kinase (JNK) and activator protein-1 cascades induced by H(2)O(2) treatment. Finally, butin exhibited protective effects against H(2)O(2)-induced apoptosis, as demonstrated by decreased apoptotic bodies, sub-G(1) hypodiploid cells and DNA fragmentation. Taken together, the protective effects of butin against H(2)O(2)-induced apoptosis were exerted via blockade of membrane potential depolarization, inhibition of the JNK pathway and mitochondria-involved caspase-dependent apoptotic pathway.
International Journal of Molecular Sciences 01/2011; 12(6):3871-87. · 2.60 Impact Factor
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ABSTRACT: Endoplasmic reticulum stress-mediated apoptosis plays an important role in the destruction of pancreatic β-cells and contributes to the development of type 1 diabetes. The present study examined the effect of KIOM-4, a mixture of four plant extracts, on streptozotocin- (STZ-) induced endoplasmic reticulum (ER) stress in rat pancreatic β-cells (RINm5F). KIOM-4 was found to inhibit STZ-induced apoptotic cell death, confirmed by formation of apoptotic bodies and DNA fragmentation. STZ was found to induce the characteristics of ER stress; mitochondrial Ca(2+) overloading, enhanced ER staining, release of glucose-regulated protein 78 (GRP78), phosphorylation of RNA-dependent protein kinase (PKR) like ER kinase (PERK) and eukaryotic initiation factor-2α (eIF-2α), cleavage of activating transcription factor 6 (ATF6) and caspase 12, and upregulation of CCAAT/enhancer-binding protein-homologous protein (CHOP). However, KIOM-4 attenuated these changes induced by STZ. Furthermore, KIOM-4 suppressed apoptosis induced by STZ in CHOP downregulated cells using CHOP siRNA. These results suggest that KIOM-4 exhibits protective effects in STZ-induced pancreatic β-cell damage, by interrupting the ER stress-mediated pathway.
Evidence-based Complementary and Alternative Medicine 01/2011; 2011. · 4.77 Impact Factor
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ABSTRACT: The ethylacetate fraction of Empetrum nigrum var. japonicum (ENE) was shown to reduce intracellular reactive oxygen species (ROS) generated by γ-radiation and activate antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and gluthathion peroxidase (GPx). ENE protected cells against radiation-induced cellular DNA damage, membrane lipid peroxidation, and protein modification, which are the main points of radiation-induced damage. In addition, ENE recovered cell viability by inhibiting apoptosis after cells were treated with radiation. ENE treatment also reduced γ-radiation induced Bax, and caspase 9 and 3 expression in irradiated cells. However, irradiated cells with ENE recovered Bcl-2 expression, which was reduced by radiation. This anti-apoptotic effect of ENE was due to the inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1)-c-Jun NH(2)-terminal kinase (JNK) cascades induced by γ-radiation. In summary, these results suggest that ENE protects cells against γ-radiation-induced oxidative stress via the reduction of ROS and attenuation of apoptosis.
The American Journal of Chinese Medicine 01/2011; 39(1):161-70. · 1.98 Impact Factor
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ABSTRACT: The protective effects of catechin 7-O-β-D glucopyranoside (C7G) against streptozotocin (STZ)-induced mitochondrial damage in rat pancreatic β-cells (RINm5F) were investigated. A marked increase in mitochondrial reactive oxygen species (ROS) was observed in STZ-treated cells; this increase was restricted by C7G treatment. C7G also scavenged superoxide anions and hydroxyl radicals generated by xanthine/xanthine oxidase (xanthine/XO) and the Fenton reaction (FeSO(4) + H(2) O(2)), respectively. C7G restored activity and expression of both mitochondrial manganese superoxide dismutase (MnSOD) and catalase (CAT), which were suppressed by STZ treatment. In addition, C7G prevented STZ-induced mitochondrial lipid peroxidation, protein carbonyl, and DNA base modification. C7G restored the loss of mitochondrial membrane potential (Δψ) that was disrupted by STZ treatment, and prevented cell death via inhibition of apoptosis. These results suggest that C7G has a protective effect against STZ-induced cell damage by its antioxidant effects and the attenuation of mitochondrial dysfunction.
Cell Biochemistry and Function 12/2010; 28(8):651-60. · 1.77 Impact Factor
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ABSTRACT: Fruits of Lycium chinense Miller (Solanaceae), distributed in northeast Asia, have gained attraction for their hepatoprotective role in traditional oriental medicine. The excessive production of reactive oxygen species (ROS) is hazardous for living organisms and damage major cellular constituents such as DNA, lipid, and protein. The cytoprotective effect of Lycium chinense fruits (Lycium extract) was assessed against H(2)O(2)-induced Chang liver cell damage.
The effect of Lycium extract against H(2)O(2)-induced cell death was determined by the MTT assay. Radical scavenging activity was determined through the assessments of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, intracellular ROS, hydroxyl radicals, and superoxide. The inductions of antioxidant enzymes were determined via their protein expressions and activities. DNA damage was measured using comet assay and expression of phospho-histone H2A.X. Lipid peroxidation was measured using 8-isoprostane level and fluorescent probe. Protein modification was measured using protein carbonyl moiety.
Lycium extract scavenged the DPPH free radicals, intracellular ROS, hydroxyl radicals, and superoxide. Lycium extract recovered activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased by H(2)O(2). Lycium extract decreased DNA damage, lipid peroxidation and protein carbonyl values increased by H(2)O(2) exposure. In addition, Lycium extract increased the cell viability of Chang liver cells exposed to H(2)O(2) via inhibition of apoptosis. These results show that Lycium extract protected Chang liver cells against oxidative stressed cell damage by H(2)O(2) via scavenging ROS and enhancing antioxidant enzyme activity.
Journal of ethnopharmacology 07/2010; 130(2):299-306. · 2.32 Impact Factor
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ABSTRACT: Sulforaphane (SFN), a dietary isothiocyanate, is a well known natural product that possesses anti-cancer and chemopreventive activities. However, the molecular mechanism of the anti-telomerase activity of SFN is not well understood. In this study, we investigated the hypothesis that SFN inhibits cell viability and telomerase activity via downregulation of telomerase reverse transcriptase (hTERT) expression. We suggest that elevated intracellular reactive oxygen species (ROS) levels, due to exposure to SFN, has a critical role in abolishing since pretreatment with NAC, an antioxidant, resulted in the recovery of hTERT expression. SFN also suppressed the phosphorylation of Akt (Ser-473), thereby inhibiting hTERT phosphorylation and this effect was reversed by pretreatment with NAC. Taken together, these data suggest that ROS are essential for the suppression of SFN-mediated telomerase activity via transcriptional and posttranslational regulation of hTERT.
Cancer letters 05/2010; 295(2):260-6. · 4.86 Impact Factor
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ABSTRACT: The objective of this study was to elucidate the cytotoxic mechanism of Compound K, with respect to the involvement of reactive oxygen species (ROS) and the mitochondrial involved apoptosis, in HT-29 human colon cancer cells. Compound K exhibited a concentration of 50% growth inhibition (IC(50)) at 20 μg/mL and cytotoxicity in a time dependent manner. Compound K produced intracellular ROS in a time dependent fashion; however, N-acetylcysteine (NAC) pretreatment resulted in the inhibition of this effect and the recovery of cell viability. Compound K induced a mitochondria-dependent apoptotic pathway via the modulation of Bax and Bcl-2 expressions, resulting in the disruption of the mitochondrial membrane potential (Δψ(m)). Loss of the Δψ(m) was followed by cytochrome c release from the mitochondria, resulting in the activation of caspase-9, -3, and concomitant poly ADP-ribosyl polymerase (PARP) cleavage, which are the indicators of caspase-dependent apoptosis. The apoptotic effect of Compound K, exerted via the activation of c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), was abrogated by specific MAPK inhibitors. This study demonstrated that Compound K-mediated generation of ROS led to apoptosis through the modulation of a mitochondria-dependent apoptotic pathway and MAPK pathway.
International Journal of Molecular Sciences 01/2010; 11(12):4916-31. · 2.60 Impact Factor
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ABSTRACT: The toxicity of formaldehyde (HCHO) has been attributed to its ability to form adducts with DNA and proteins. Triphlorethol-A, derived from Ecklonia cava, was reported to exert a cytoprotective effect against oxidative stress damage via an antioxidant mechanism. The aim of this study was to examine the mechanisms underlying the triphlorethol-A ability to protect Chinese hamster lung fibroblast (V79-4) cells against HCHO-induced damage. Triphlorethol-A significantly decreased the HCHO-induced intracellular reactive oxygen species (ROS) production. Triphlorethol-A prevented increased cell damage induced by HCHO via inhibition of mitochondria-mediated caspase-dependent apoptosis pathway. Triphlorethol-A diminished HCHO-induced mitochondrial dysfunction, including loss of mitochondrial membrane action potential (Δψ) and adenosine triphosphate (ATP) depletion. Furthermore, the anti-apoptotic effect of triphlorethol-A was exerted through inhibition of c-Jun NH(2)-terminal kinase (JNK), which was enhanced by HCHO. Our data indicate that triphlorethol-A exerts a cytoprotective effect in V79-4 cells against HCHO-induced oxidative stress by inhibiting the mitochondria-mediated caspase-dependent apoptotic pathway.
Journal of Toxicology and Environmental Health Part A 01/2010; 73(21-22):1477-89. · 1.83 Impact Factor
