Lanatoside C suppressed colorectal cancer cell growth by inducing mitochondrial dysfunction and increased radiation sensitivity by impairing DNA damage repair
DC Field | Value | Language |
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dc.contributor.author | Kang, Mi Ae | - |
dc.contributor.author | Kim, Mi-Sook | - |
dc.contributor.author | Kim, Wonwoo | - |
dc.contributor.author | Um, Jee-Hyun | - |
dc.contributor.author | Shin, Young-Joo | - |
dc.contributor.author | Song, Jie-Young | - |
dc.contributor.author | Jeong, Jae-Hoon | - |
dc.date.available | 2020-02-28T02:45:14Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2016-02-02 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/8559 | - |
dc.description.abstract | Cardiac glycosides are clinically used for cardiac arrhythmias. In this study, we investigated the mechanism responsible for anti-cancer and radiosensitizing effects of lanatoside C in colorectal cancer cells. Lanatoside C-treated cells showed classic patterns of autophagy, which may have been caused by lanatoside C-induced mitochondrial aggregation or degeneration. This mitochondrial dysfunction was due to disruption of K+ homeostasis, possibly through inhibition of Na+/K+-ATPase activity. In addition, lanatoside C sensitized HCT116 cells (but not HT-29 cells) to radiation in vitro. gamma-H2AX, a representative marker of DNA damage, were sustained longer after combination of irradiation with lanatoside C, suggesting lanatoside C impaired DNA damage repair processes. Recruitment of 53BP1 to damaged DNA, a critical initiation step for DNA damage repair signaling, was significantly suppressed in lanatoside C-treated HCT116 cells. This may have been due to defects in the RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A that increases 53BP1 recruitment to DNA damage sites. Although lanatoside C alone reduced tumor growth in the mouse xenograft tumor model, combination of lanatoside C and radiation inhibited tumor growth more than single treatments. Thus, lanatoside C could be a potential molecule for anti-cancer drugs and radiosensitizing agents. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | IMPACT JOURNALS LLC | - |
dc.relation.isPartOf | ONCOTARGET | - |
dc.subject | CARDIAC-GLYCOSIDES | - |
dc.subject | ANTICANCER AGENT | - |
dc.subject | NA+/K+-ATPASE | - |
dc.subject | AUTOPHAGY | - |
dc.subject | INHIBITION | - |
dc.subject | APOPTOSIS | - |
dc.subject | OUABAIN | - |
dc.subject | DEATH | - |
dc.subject | 53BP1 | - |
dc.subject | RNF8 | - |
dc.title | Lanatoside C suppressed colorectal cancer cell growth by inducing mitochondrial dysfunction and increased radiation sensitivity by impairing DNA damage repair | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000369952800070 | - |
dc.identifier.doi | 10.18632/oncotarget.6832 | - |
dc.identifier.bibliographicCitation | ONCOTARGET, v.7, no.5, pp.6074 - 6087 | - |
dc.identifier.scopusid | 2-s2.0-84958073947 | - |
dc.citation.endPage | 6087 | - |
dc.citation.startPage | 6074 | - |
dc.citation.title | ONCOTARGET | - |
dc.citation.volume | 7 | - |
dc.citation.number | 5 | - |
dc.contributor.affiliatedAuthor | Um, Jee-Hyun | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | lanatoside C | - |
dc.subject.keywordAuthor | autophagy | - |
dc.subject.keywordAuthor | mitochondria | - |
dc.subject.keywordAuthor | DNA damage repair | - |
dc.subject.keywordAuthor | radiosensitivity | - |
dc.subject.keywordPlus | CARDIAC-GLYCOSIDES | - |
dc.subject.keywordPlus | ANTICANCER AGENT | - |
dc.subject.keywordPlus | NA+/K+-ATPASE | - |
dc.subject.keywordPlus | AUTOPHAGY | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | OUABAIN | - |
dc.subject.keywordPlus | DEATH | - |
dc.subject.keywordPlus | 53BP1 | - |
dc.subject.keywordPlus | RNF8 | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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