Synthetic 8-hydroxydeoxyguanosine inhibited metastasis of pancreatic cancer through concerted inhibitions of ERM and Rho-GTPase
DC Field | Value | Language |
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dc.contributor.author | Park, Jong-Min | - |
dc.contributor.author | Han, Young-Min | - |
dc.contributor.author | Jeong, Migyeong | - |
dc.contributor.author | Chung, Myung Hee | - |
dc.contributor.author | Kwon, Chang Il | - |
dc.contributor.author | Ko, Kwang Hyun | - |
dc.contributor.author | Hahm, Ki Baik | - |
dc.date.available | 2020-02-27T17:42:22Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2017-09 | - |
dc.identifier.issn | 0891-5849 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/5724 | - |
dc.description.abstract | 8-hydroxydeoxyguanosine (8-OHdG) is generated consequent to oxidative stress, but its paradoxical anti-oxidative, anti-inflammatory, and anti-mutagenic effects via Rho-GTPase inhibition were noted in various models of inflammation and cancer. Metastasis occurs through cell detachment, epithelial-mesenchymal transition (EMT), and cell migration; during these processes, changes in cell morphology are initiated through Rho-GTPase-dependent actin cytoskeleton polymerization. In this study, we explored the anti-metastatic mechanisms of 8OHdG in Panc-1 pancreatic cancer cells. 8-OHdG inhibits cell migration by inactivating ERM and Rho-GTPase proteins, and inhibiting focal adhesion kinase (FAK) and matrix metalloproteinases (MMPs). At 15 min, 8-OHdG significantly inactivated ERM (p<0.05) and led to a significant retardation of wound healing; siERM and H1152 (ROCK inhibitor) had similar effects (p<0.05). However, FAK inhibitor 14, DPI (NOX inhibitor), and NAC (antioxidant) significantly delayed wound healing without inhibiting ERM or CD44 (p<0.05). In the experiments on cell migration, siERM, siCD44, DPI, and 8-OHdG significantly inhibited MMPs. 8-OHdG significantly decreased DCF-DA activation in Panc-1 pancreatic cancer cells and down-regulated NOXs (nox-1, nox-2, and nox-3). Finally, all of these anti-migration actions of 8-OHdG resulted in significant inhibition of EMT, as evidenced by the up-regulation of ZO-1 and claudin-1 and down-regulation of vimentin. We found significant inhibition of lung metastasis of Panc-1 cells by 8-OHdG. In conclusion, exogenous 8-OHdG had potent anti-metastasis effects mediated by either ERM or Rho GTPase inhibition in metastasis-prone pancreatic cancer cells. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCIENCE INC | - |
dc.relation.isPartOf | FREE RADICAL BIOLOGY AND MEDICINE | - |
dc.subject | MATRIX METALLOPROTEINASES | - |
dc.subject | BREAST-CANCER | - |
dc.subject | ADHESION | - |
dc.subject | INVASION | - |
dc.subject | PROTEIN | - |
dc.subject | EXPRESSION | - |
dc.subject | ACTIVATION | - |
dc.subject | MIGRATION | - |
dc.subject | PREDICTS | - |
dc.subject | STRESS | - |
dc.title | Synthetic 8-hydroxydeoxyguanosine inhibited metastasis of pancreatic cancer through concerted inhibitions of ERM and Rho-GTPase | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000406049200015 | - |
dc.identifier.doi | 10.1016/j.freeradbiomed.2017.06.003 | - |
dc.identifier.bibliographicCitation | FREE RADICAL BIOLOGY AND MEDICINE, v.110, pp.151 - 161 | - |
dc.identifier.scopusid | 2-s2.0-85020683780 | - |
dc.citation.endPage | 161 | - |
dc.citation.startPage | 151 | - |
dc.citation.title | FREE RADICAL BIOLOGY AND MEDICINE | - |
dc.citation.volume | 110 | - |
dc.contributor.affiliatedAuthor | Chung, Myung Hee | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | 8-hydroxydeoxyguanosine | - |
dc.subject.keywordAuthor | ERM | - |
dc.subject.keywordAuthor | EMT | - |
dc.subject.keywordAuthor | Metastasis | - |
dc.subject.keywordAuthor | Pancreatic cancer | - |
dc.subject.keywordPlus | MATRIX METALLOPROTEINASES | - |
dc.subject.keywordPlus | BREAST-CANCER | - |
dc.subject.keywordPlus | ADHESION | - |
dc.subject.keywordPlus | INVASION | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | MIGRATION | - |
dc.subject.keywordPlus | PREDICTS | - |
dc.subject.keywordPlus | STRESS | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Endocrinology & Metabolism | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Endocrinology & Metabolism | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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