We investigated the cytoprotective effect of phloroglucinol, which was isolated from Ecklonia cava (brown alga), against oxidative stress induced cell damage in Chinese hamster lung fibroblast (V79-4) cells. Phloroglucinol was found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydrogen peroxide (H(2)O(2)), hydroxy radical, intracellular reactive oxygen species (ROS), and thus prevented lipid peroxidation. As a result, phloroglucinol reduced H(2)O(2) induced apoptotic cells formation in V79-4 cells. In addition, phloroglucinol inhibited cell damage induced by serum starvation and radiation through scavenging ROS. Phloroglucinol increased the catalase activity and its protein expression. In addition, catalase inhibitor abolished the protective effect of phloroglucinol from H(2)O(2) induced cell damage. Furthermore, phloroglucinol increased phosphorylation of extracellular signal regulated kinase (ERK). Taken together, the results suggest that phloroglucinol protects V79-4 cells against oxidative damage by enhancing the cellular catalase activity and modulating ERK signal pathway.

We have investigated the cytoprotective effect of eckol, which was isolated from Ecklonia cava, against oxidative stress induced cell damage in Chinese hamster lung fibroblast (V79-4) cells. Eckol was found to scavenge 1,1-diphenyl-2-picrylhydrazyl radical, hydrogen peroxide (H 2 O 2 ), hydroxy radical, intracellular reactive oxygen species (ROS), and thus prevented lipid peroxidation. As a result, eckol reduced H 2 O 2 induced cell death in V79-4 cells. In addition, eckol inhibited cell damage induced by serum starvation and radiation by scavenging ROS. Eckol was found to increase the activity of catalase and its protein expression. Further, molecular mechanistic study revealed that eckol increased phosphorylation of extracellular signal-regulated kinase and activity of nuclear factor j B. Taken together, the results suggest that eckol protects V79-4 cells against oxidative damage by enhancing the cellular antioxidant activity and modulating cellular signal pathway.

Pretreatment of NCI-H460 human lung cancer cells with compound K produced by intestinal bacteria enhances gamma-ray radiation-induced cell death. Increases in apoptosis induced by combined treatment are made apparent in the observation of nuclear fragmentation, loss of mitochondrial membrane potential (Deltapsi), and activation of caspase 3. Apoptosis induced by compound K and gamma-ray radiation is associated with reactive oxygen species (ROS) generation. Furthermore, compound K, in combination with gamma-ray radiation, has an enhanced effect in the regression of NCI-H460 tumor xenografts of nude mice. These results suggest that compound K has possible application for cancer therapy when used in combination with gamma-ray radiation.

Aim: To investigate the anti-oxidant properties of esculetin (6,7-dihydroxycoumarin) against H 2 O 2 -induced Chinese hamster lung fibroblast (V79-4) damage. Methods: The radical scavenging activity was assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydroxyl radical, and intracellular reactive oxygen species (ROS). In addition, lipid peroxidation was assayed by the measure of related substances which react with thiobarbituric acid. The amount of carbonyl formation in protein was determined using a protein carbonyl ELISA kit. As well, cellular DNA damage was detected by Western blot and immunofluorescence image. Cell viability was assessed by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay. Results: Esculetin exhibited DPPH radical scavenging, hydroxyl radical scavenging, and intracellular ROS scavenging activities. The radical scavenging activity of esculetin resulted in the protection of cells from lipid peroxidation, protein carbonyl, and DNA damage induced by H 2 O 2 . Therefore, esculetin recovered cell viability exposed to H 2 O 2 . Conclusion: Esculetin efficiently attenuated the oxidative stress induced cell damage via its anti-oxidant properties. As a result, esculetin may be useful in the development of functional food and raw materials of medicine.

In the present study, triphlorethol-A, a phlorotannin, was isolated from Ecklonia cava and its antioxidant properties were investigated. Triphlorethol-A was found to scavenge intracellular reactive oxygen species (ROS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and thus prevented lipid peroxidation. The radical scavenging activity of triphlorethol-A protected the Chinese hamster lung fibroblast (V79-4) cells exposed to hydrogen peroxide (H2O2) against cell death, via the activation of ERK protein. Furthermore, triphlorethol-A reduced the apoptotic cells formation induced by H2O2. Triphlorethol-A increased the activities of cellular antioxidant enzymes like, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Hence, from the present study, it is suggestive that triphlorethol-A protects V79-4 cells against H2O2 damage by enhancing the cellular antioxidative activity.

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Fisetin (3,3',4',7-tetrahydroxyflavone), a dietary flavonoid compound, is currently being investigated for its anticancer effect in various cancer models, including lung cancer. Recent studies show that fisetin induces cell growth inhibition and apoptosis in the human non-small cell lung cancer line NCI-H460. In this study, we investigated whether fisetin can induce endoplasmic reticulum (ER) stress-mediated apoptosis in NCI-H460 cells. Fisetin induced mitochondrial reactive oxygen species (ROS) and characteristic signs of ER stress: ER staining; mitochondrial Ca(2+) overload; expression of ER stress-related proteins; glucose-regulated protein (GRP)-78, phosphorylation of protein kinase RNA (PKR)-like endoplasmic reticulum kinase (PERK) and phosphorylation of eukaryotic initiation factor-2 α subunit; cleavage of activating transcription factor-6; phosphorylation of inositol-requiring kinase-1 and splicing of X-box transcription factor-1; induction of C/EBP homologous protein and cleaved caspase-12. siRNA-mediated knockdown of CHOP and ATF-6 attenuated fisetin-induced apoptotic cell death. In addition, fisetin induced phosphorylation of ERK, JNK, and p38 MAPK. Moreover, silencing of the MAPK signaling pathway prevented apoptotic cell death. In summary, our results indicate that, in NCI-H460 cells, fisetin induces apoptosis and ER stress that is mediated by induction of the MAPK signaling pathway.

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