Cited 26 times in
Caspase-4 is essential for saikosaponin a-induced apoptosis acting upstream of caspase-2 and γ-H2AX in colon cancer cells
DC Field | Value | Language |
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dc.contributor.author | 김병모 | - |
dc.contributor.author | 조소영 | - |
dc.date.accessioned | 2019-01-10T16:40:22Z | - |
dc.date.available | 2019-01-10T16:40:22Z | - |
dc.date.issued | 2017 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/166584 | - |
dc.description.abstract | Saikosaponin a (SSa), a bioactive phytochemical from Bupleurum, triggers sequential caspase-2 and caspase-8 activation, and thereby induces caspase-mediated apoptosis in human colon carcinoma (HCC) cells. However, the upstream mechanism of caspase-2 activation remains unknown. Therefore, we investigated the signaling mechanisms underlying SSa-induced caspase activation and apoptosis in HCC cells. SSa treatment triggered marked antitumor effects, especially in HCC cells, in a cell culture model and a mouse xenograft model. SSa also induced the activation of several endoplasmic reticulum (ER) stress signals. Specifically, caspase-4, a critical regulator of ER stress-induced apoptosis, was activated significantly after SSa treatment. Mechanistically, selective inhibition of caspase-4 suppressed SSa-induced apoptosis, colony inhibition, and the activation of caspase-3, -8, and -2, but not vice versa. Consistent with the important role of caspase-2 in the DNA damage response, SSa induced DNA damage, as evidenced by a cytokinesis-block micronucleus assay, single-cell gel electrophoresis, and an increase in the levels of γ-H2AX, a DNA damage marker. Moreover, inhibition of caspase-4 activation inhibited SSa-induced histone H2AX phosphorylation. Taken together, these results suggest that caspase-4 is an upstream regulator of SSa-induced DNA damage and caspase activation in HCC cells. Given that SSa-induced apoptosis appeared to be specific to certain cell types including HCC cells, SSa may be a promising cancer therapy agent in certain types of cancer. | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | English | - |
dc.publisher | Impact Journals | - |
dc.relation.isPartOf | ONCOTARGET | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Caspase-4 is essential for saikosaponin a-induced apoptosis acting upstream of caspase-2 and γ-H2AX in colon cancer cells | - |
dc.type | Article | - |
dc.contributor.college | Research Institutes (연구소) | - |
dc.contributor.department | Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) | - |
dc.contributor.googleauthor | Su Jin Kang | - |
dc.contributor.googleauthor | Young Joon Lee | - |
dc.contributor.googleauthor | Sung Gu Kang | - |
dc.contributor.googleauthor | Soyoung Cho | - |
dc.contributor.googleauthor | Wonsuck Yoon | - |
dc.contributor.googleauthor | Ji Hong Lim | - |
dc.contributor.googleauthor | Sang-Hyun Min | - |
dc.contributor.googleauthor | Tae Ho Lee | - |
dc.contributor.googleauthor | Byeong Mo Kim | - |
dc.identifier.doi | 10.18632/oncotarget.22247 | - |
dc.contributor.localId | A00497 | - |
dc.contributor.localId | A03840 | - |
dc.relation.journalcode | J02421 | - |
dc.identifier.eissn | 1949-2553 | - |
dc.identifier.pmid | 29245990 | - |
dc.subject.keyword | DNA damage | - |
dc.subject.keyword | caspase-4 | - |
dc.subject.keyword | endoplasmic reticulum (ER) stress | - |
dc.subject.keyword | human colon carcinoma (HCC) | - |
dc.subject.keyword | saikosaponin a (SSa) | - |
dc.contributor.alternativeName | Kim, Byeong Mo | - |
dc.contributor.affiliatedAuthor | 김병모 | - |
dc.contributor.affiliatedAuthor | 조소영 | - |
dc.citation.volume | 8 | - |
dc.citation.number | 59 | - |
dc.citation.startPage | 100433 | - |
dc.citation.endPage | 100448 | - |
dc.identifier.bibliographicCitation | ONCOTARGET, Vol.8(59) : 100433-100448, 2017 | - |
dc.identifier.rimsid | 60322 | - |
dc.type.rims | ART | - |
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