Cordycepin promotes apoptosis in renal carcinoma cells by activating the MKK7-JNK signaling pathway through inhibition of c-FLIPL expression
DC Field | Value | Language |
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dc.contributor.author | Hwang, In-Hu | - |
dc.contributor.author | Oh, Seung Yoon | - |
dc.contributor.author | Jang, Hyun-Jin | - |
dc.contributor.author | Jo, Eunbi | - |
dc.contributor.author | Joo, Jong Cheon | - |
dc.contributor.author | Lee, Kyung-Bok | - |
dc.contributor.author | Yoo, Hwa-Seung | - |
dc.contributor.author | Lee, Mi Young | - |
dc.contributor.author | Park, Soo Jung | - |
dc.contributor.author | Jang, Ik-Soon | - |
dc.date.accessioned | 2021-09-03T00:06:11Z | - |
dc.date.available | 2021-09-03T00:06:11Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2017-10-18 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/81882 | - |
dc.description.abstract | Cellular FLICE inhibitory protein (c-FLIP) is a key anti-apoptotic regulator that associates with the signaling complex downstream of NF-kappa B, negatively interfering with apoptotic signaling. The role of c-FLIP downregulation by negative regulation of NF-kappa B signaling during apoptosis is poorly understood. Here, we demonstrate that NF-kappa B-mediated c-FLIPL negatively regulates the JNK signaling pathway, and that cordycepin treatment of human renal cancer cells leads to apoptosis induction through c-FLIPL inhibition. TNF-alpha-induced inflammatory microenvironments stimulated NF-kappa B signaling and the c-FLIP long form (c-FLIPL) in TK-10 cells. Specifically, cordycepin inhibited TNF-alpha-mediated NF-kappa B activation, which induced renal cancer cell apoptosis. Cordycepin downregulated GADD45B and c-FLIPL, but upregulated MKK7 and phospho-JNK, by preventing nuclear mobilization of NF-kappa B. Furthermore, siRNA-mediated knockdown of GADD45B in cordycepin-treated TK-10 cells considerably increased MKK7 compared to cordycepin alone. siRNA-mediated knockdown of cFLIP(L) prevented TNF-a-induced JNK inactivation, whereas c-FLIPL overexpression inhibited cordycepin-mediated JNK activation. The JNK inhibitor SP600125 strongly inhibited Bax expression. In nude mice, cordycepin significantly decreased tumor volume. Taken together, the results indicate that cordycepin inhibits TNF-a-mediated NF-kappa B/GADD45B signaling, which activates the MKK7-JNK signaling pathway through inhibition of c-FLIPL expression, thus inducing TK-10 cell apoptosis. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.subject | NF-KAPPA-B | - |
dc.subject | NITRIC-OXIDE PRODUCTION | - |
dc.subject | IN-VIVO | - |
dc.subject | JNK | - |
dc.subject | CANCER | - |
dc.subject | INFLAMMATION | - |
dc.subject | KINASE | - |
dc.subject | PHOSPHORYLATION | - |
dc.subject | SUPPRESSION | - |
dc.subject | ANTICANCER | - |
dc.title | Cordycepin promotes apoptosis in renal carcinoma cells by activating the MKK7-JNK signaling pathway through inhibition of c-FLIPL expression | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Hwang, In-Hu | - |
dc.identifier.doi | 10.1371/journal.pone.0186489 | - |
dc.identifier.scopusid | 2-s2.0-85031933716 | - |
dc.identifier.wosid | 000413168100064 | - |
dc.identifier.bibliographicCitation | PLOS ONE, v.12, no.10 | - |
dc.relation.isPartOf | PLOS ONE | - |
dc.citation.title | PLOS ONE | - |
dc.citation.volume | 12 | - |
dc.citation.number | 10 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | NITRIC-OXIDE PRODUCTION | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | JNK | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | KINASE | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | SUPPRESSION | - |
dc.subject.keywordPlus | ANTICANCER | - |
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