Caspase-4 is essential for saikosaponin a-induced apoptosis acting upstream of caspase-2 and gamma-H2AX in colon cancer cells
DC Field | Value | Language |
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dc.contributor.author | Kang, Su Jin | - |
dc.contributor.author | Lee, Young Joon | - |
dc.contributor.author | Kang, Sung Gu | - |
dc.contributor.author | Cho, Soyoung | - |
dc.contributor.author | Yoon, Wonsuck | - |
dc.contributor.author | Lim, Ji Hong | - |
dc.contributor.author | Min, Sang-Hyun | - |
dc.contributor.author | Lee, Tae Ho | - |
dc.contributor.author | Kim, Byeong Mo | - |
dc.date.accessioned | 2021-09-02T23:00:33Z | - |
dc.date.available | 2021-09-02T23:00:33Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2017-11-21 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/81521 | - |
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 gamma-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.language | English | - |
dc.language.iso | en | - |
dc.publisher | IMPACT JOURNALS LLC | - |
dc.subject | ENDOPLASMIC-RETICULUM STRESS | - |
dc.subject | DNA-DAMAGE RESPONSE | - |
dc.subject | HISTONE H2AX | - |
dc.subject | GROWTH-INHIBITION | - |
dc.subject | PROTEIN-SYNTHESIS | - |
dc.subject | KINASE PERK | - |
dc.subject | ACTIVATION | - |
dc.subject | INVOLVEMENT | - |
dc.subject | DEATH | - |
dc.subject | PHOSPHORYLATION | - |
dc.title | Caspase-4 is essential for saikosaponin a-induced apoptosis acting upstream of caspase-2 and gamma-H2AX in colon cancer cells | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kang, Sung Gu | - |
dc.contributor.affiliatedAuthor | Yoon, Wonsuck | - |
dc.identifier.doi | 10.18632/oncotarget.22247 | - |
dc.identifier.scopusid | 2-s2.0-85034634115 | - |
dc.identifier.wosid | 000419561600105 | - |
dc.identifier.bibliographicCitation | ONCOTARGET, v.8, no.59, pp.100433 - 100448 | - |
dc.relation.isPartOf | ONCOTARGET | - |
dc.citation.title | ONCOTARGET | - |
dc.citation.volume | 8 | - |
dc.citation.number | 59 | - |
dc.citation.startPage | 100433 | - |
dc.citation.endPage | 100448 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | ENDOPLASMIC-RETICULUM STRESS | - |
dc.subject.keywordPlus | DNA-DAMAGE RESPONSE | - |
dc.subject.keywordPlus | HISTONE H2AX | - |
dc.subject.keywordPlus | GROWTH-INHIBITION | - |
dc.subject.keywordPlus | PROTEIN-SYNTHESIS | - |
dc.subject.keywordPlus | KINASE PERK | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | INVOLVEMENT | - |
dc.subject.keywordPlus | DEATH | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordAuthor | saikosaponin a (SSa) | - |
dc.subject.keywordAuthor | human colon carcinoma (HCC) | - |
dc.subject.keywordAuthor | endoplasmic reticulum (ER) stress | - |
dc.subject.keywordAuthor | caspase-4 | - |
dc.subject.keywordAuthor | DNA damage | - |
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