Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00369 (ROS)
 19,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Doxorubicin is an effective anthracycline used for cancer therapy. However, the clinical application of doxorubicin has been largely limited by its irreversible cardiotoxicity, which is mainly induced by the primary amine group. In this study, we structurally modified doxorubicin by converting the primary amine into an acid-labile amide before assessing the acute cardiac effect of doxorubicin (pristine or modified) on cardiomyocyte contractile function. Contractile properties of murine cardiomyocytes were analyzed including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)) and maximal velocity of shortening/re-lengthening (+/-dL/dt). Cell toxicity and survival rate were evaluated using the MTT assay. The doxorubicin-free base was amidized by reacting with 3,4,5,6-tetrahydophthalic anhydride (THPA) or 3,3,4,4-tetramethylsuccinic anhydride (TMSA) to yield doxorubicin-THPA or -TMSA. Acute exposure of pristine doxorubicin (10(-9)-10(-5)M) for 30 min significantly prolonged TPS and TR(90) without affecting PS and +/-dL/dt. Interestingly, doxorubicin-induced prolongation of TPS and TR(90) was significantly attenuated or abrogated by amidization of doxorubicin. Neither doxorubicin-THPA nor -TMSA affected PS and +/-dL/dt. ROS and MTT assay revealed significantly reduced ROS production and cardiac cell toxicity from amidized doxorubicin compared with the pristine compound. Comparable cytotoxicity in human ovarian cancer SKOV-3 cells was observed between amidized and pristine doxorubicin compounds. These data provide evidence for the first time that structural modification of doxorubicin alleviates its cardiac toxicity.
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PMID:Amidization of doxorubicin alleviates doxorubicin-induced contractile dysfunction and reduced survival in murine cardiomyocytes. 1846 42

The influence of dendroflorin, a potentially active compound extracted from Dendrobium nobile, on cell growth and cell cycles was assessed in a human embryo lung fibroblastic MRC-5 cell line. An MTT assay indicated that dendroflorin benefits cell proliferation. Additionally, we used flow cytometry to examine the cell cycles in senescent MRC-5 cells after treatment with dendroflorin, discovering that dendroflorin could trigger cells in the G1 phase to enter the S phase. Further examination of intracellular ROS contents using DCFH-DA suggested that dendroflorin helps ROS degradation, partly elucidating the mechanism of its effects. All of the above results suggest that dendroflorin is a potential candidate with anti-senescence activity.
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PMID:Dendroflorin retards the senescence of MRC-5 cells. 1846 96

Polyamine-naphthoquinone conjugates 5a-c were synthesized by nucleophilic displacement of 2-methoxy-lawsone 3a, 2-methoxylapachol 3b and 2-methoxy-nor-lapachol 3c with the polyamine N1-Boc-N5-Bn-spermidine 4. Unprotected derivatives 6a-c were synthesized to evaluate the effect of the protective Boc group on the activity of compounds 5a-c. The colorimetric MTT assay was used to evaluate their cytotoxic activity. All compounds were active against human lines of promyelocytic leukemia (HL-60), lung cancer (GLC4), Burkitt lymphoma (Daudi) and a mouse breast tumor (Ehrlich carcinoma), but only unprotected 6a-c showed activity against the human line of melanoma (MV-3). IC50 values were obtained from dose response curves by linear regression. DNA fragmentation was measured by quantification of the subG1 peak of the cell cycle. Apoptosis of HL-60 treated with 5c was dose-dependent. The amount of DNA fragmentation observed by exposure of HL-60 to 25 microM of compounds 5a-c and 6a-c is compatible with the decrease in viability induced by the drugs at this concentration. Production of ROS was measured by H2-CFDA. Kinetics of HL-60 DNA fragmentation and ROS formation by 5c indicated that production of ROS precedes cell death. In conclusion, spermidine-1,4-naphthoquinone conjugates exhibited an increase in activity compared with the natural products and induced apoptosis of tumor cell lines by a mechanism that is mediated, at least in part, by ROS production.
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PMID:Antitumoral activity of new polyamine-naphthoquinone conjugates. 1857 41

This study is to examine the effects of equol on the H(2)O(2)-induced death of bovine aortic endothelial cells (bAECs) and the mechanism of its protective effects. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] assay showed that in the control group, cell survival rate decreased significantly, each in proportion to the duration of the H(2)O(2) stimulation (P<0.05), but, in the equol-pretreated group, such decrease was not statistically significant. After Hoechst 33342 staining, in the equol-pretreated group the number of cells with apoptotic morphology decreased significantly. Equol pretreatment effectively inhibited the H(2)O(2)-induced cell death by the reduction of intracellular ROS production (P<0.05). Incubation of bAECs with equol increased the expression of phospho-p38 MAPK and Bcl-2 after the H(2)O(2) exposure compared with their expression without the equol pretreatment. Furthermore, SB203580 inhibited phospho-p38 MAPK expression and increased apoptotic cell death. This study proves equol has a significant antioxidant effect on the bAECs that were exposed to H(2)O(2).
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PMID:Antioxidant effects of equol on bovine aortic endothelial cells. 1870 29

Saffron (dried stigmas of Crocus sativus L.) has been used as a spice, food colorant and medicinal plant for millennia. In this study cytotoxic effect of saffron extract was evaluated in HepG2 and HeLa cell lines. Meanwhile role of apoptosis and ROS were explored. Malignant and non-malignant cells (L929) were cultured in DMEM medium and incubated with different concentrations of ethanolic saffron extract. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). ROS was measured using DCF-DA by flow cytometry analysis. Saffron could decrease cell viability in malignant cells as a concentration and time-dependent manner. The IC50 values against HeLa and HepG2 were determined 800 and 950 microg/ml after 48 h, respectively. Saffron induced a sub-G1 peak in flow cytometry histogram of treated cells compared to control indicating apoptotic cell death is involved in saffron toxicity. This toxicity was also independent of ROS production. It might be concluded that saffron could cause cell death in HeLa and HepG2 cells, in which apoptosis or programmed cell death plays an important role. Saffron could be also considered as a promising chemotherapeutic agent in cancer treatment in future.
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PMID:Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines. 1879 Jul 14

Barley is a major crop worldwide. It has been reported that barley seeds have an effect on scavenging ROS. However, little has been known about the functional role of the barley on the inhibition of DNA damage and apoptosis by ROS. In this study, we purified 3,4-dihydroxybenzaldehyde from the barley with silica gel column chromatography and HPLC and then identified it by GC/MS. And we firstly investigated the inhibitory effects of 3,4-dihydroxybenzaldehyde purified from the barley on oxidative DNA damage and apoptosis induced by H(2)O(2), the major mediator of oxidative stress and a potent mutagen. In antioxidant activity assay such as DPPH radical and hydroxyl radical scavenging assay, Fe(2+) chelating assay, and intracellular ROS scavenging assay by DCF-DA, 3,4-dihydroxybenzaldehyde was found to scavenge DPPH radical, hydroxyl radical and intracellular ROS. Also it chelated Fe(2+). In in vitro oxidative DNA damage assay and the expression level of phospho-H2A.X, it inhibited oxidative DNA damage and its treatment decreased the expression level of phospho-H2A.X. And in oxidative cell death and apoptosis assay via MTT assay and Hoechst 33342 staining, respectively, the treatment of 3,4-dihydroxybenzaldehyde attenuated H(2)O(2)-induced cell death and apoptosis. These results suggest that the barley may exert the inhibitory effect on H(2)O(2)-induced tumor development by blocking H(2)O(2)-induced oxidative DNA damage, cell death and apoptosis.
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PMID:3,4-dihydroxybenzaldehyde purified from the barley seeds (Hordeum vulgare) inhibits oxidative DNA damage and apoptosis via its antioxidant activity. 1902 39

Exploration of antioxidants of plant origin and scientific validation of their efficacies has unraveled bioactives from natural sources. In this study, two terpenoids camphene and geraniol were assessed for their cytoprotective and antioxidant potential using t-BHP stressed rat alveolar macrophages. Effect of these test substances along with a known plant derived antioxidant quercetin was seen on cell viability, some oxidative stress markers as well as on mitochondrial membrane potential. Both the test substances geraniol and camphene increased the cell viability significantly as indicated by MTT assay and LDH release assay, during pre-treatment of test compound. Camphene and geraniol showed 29% (P<0.05) and 45% (P<0.05) increase in SOD activity, 28% and 120% (P<0.001) increase in GSH content and restored the mitochondrial membrane potential during pre-treatment as compared to stressed cells. Camphene and geraniol were found to significantly decrease lipid peroxidation, inhibit NO release (83.84% and 64.61%) and ROS generation in the pre-treated cells as compared to stressed cells. The test compounds also showed significant protection against ROS during post-treatment of the test compounds. Results indicate the pharmacological potential of these phytochemicals in lung inflammatory diseases where oxidative stress is a critical control point.
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PMID:Plant derived antioxidants - Geraniol and camphene protect rat alveolar macrophages against t-BHP induced oxidative stress. 1913 18

This study assessed the effect of 20 and 6% ambient oxygen (O(2)) or 5-50 micromol/l hydrogen peroxide (H(2)O(2)) on apoptosis, necrosis, proliferation and fusion of BeWo cells. The expression of p53, Mdm2 and Bax was assessed by western blotting. Apoptosis was increased in cells cultured in 6% O(2) tension and 50 micromol/l H(2)O(2) (P < 0.05, P < 0.01 by ADP:ATP ratio). In the same conditions, cell viability as estimated by the MTT assay was decreased (6% O(2) P < 0.01, 50 micromol/l H(2)O(2) P < 0.05). Human chorionic gonadotrophin secretion was decreased by culture in 6%O(2) and 50 micromol/l H(2)O(2) (P < 0.05). Cell fusion was also decreased by treatment with 50 micromol/l H(2)O(2) (P < 0.05). Treatment with 50 micromol/l H(2)O(2) was associated with increased expression of p53 and decreased expression of Mdm2 (P < 0.05). This study provides evidence that BeWo cell turnover is altered following exposure to hypoxia or ROS. It is concluded that BeWo cell culture is an appropriate model for investigating the regulation of trophoblast cell turnover. In addition, these data support a role for p53 in mediating altered trophoblast cell turnover in response to oxidative stress.
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PMID:Does altered oxygenation or reactive oxygen species alter cell turnover of BeWo choriocarcinoma cells? 1914 77

The effect of gadolinium chloride (Gd) on the proliferation of HeLa cells was investigated at lower concentration. The results obtained by MTT and cell cycle analysis showed that Gd promoted proliferation by inducing S phase entry in HeLa cells at the concentration less than 100 microM. It was further evidenced by both an increase in the levels of phosphorylation of retinoblastoma protein (pRb) and a remarkable increase in cyclin E expression. Moreover, the survival of cells, exposed to Gd up to 3-5 days, was increased compared with control. The attenuation of the serum deprivation-induced cell loss by Gd was associated with the sustained activation of FAK (PY(397)) and the delayed activation of JNKs pathway. Besides, it appeared that Gd promoted cell proliferation and survival in HeLa cells was not contributed to the ROS generation. Based on the present results, both positive and negative effects of the lanthanides as potential drugs or diagnostic agents are discussed.
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PMID:Gadolinium promoted proliferation and enhanced survival in human cervical carcinoma cells. 1918 57

Keloids are benign skin tumors and are the effect of a dysregulated wound-healing process in genetically predisposed patients. They are characterized by formation of excess scar tissue beyond the boundaries of the wound. Keloids are often confused with hypertrophic scars because of an apparent lack of morphologic differences. The molecular distinction between scars and keloid is still controversial and, until today, there is no appropriate treatment yet for keloid disease. In this study, we have found, for the first time, p53 mutations in both hypertrophic scar and keloids fibroblasts from cultured cells to various extents. Since p53 plays a central role in the DNA damage response by inducing cell cycle arrest and/or apoptotic cell death, we also set up time course experiments making cell cultures at different times to investigate the phenomenon of apoptosis and its involvement in the process of pathological scarring in both hypertrophic scars and keloids. The extent of apoptosis in this study was investigated by DNA fragmentation and MTT assays, propidium iodide staining, p53 expression, and subcellular distribution. Moreover, the correlation of apoptosis and ROS levels in keloid and hypertrophic scars fibroblasts was assessed. Understanding the molecular mechanisms that determine the regulation of apoptosis during wound healing might allow us to therapeutically modulate these pathways so that apoptotic cell death is reactivated in dysregulated and hypertrophic cells.
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PMID:Differential apoptosis markers in human keloids and hypertrophic scars fibroblasts. 1922 35


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