JNC-1043, a Novel Podophyllotoxin Derivative, Exerts Anticancer Drug and Radiosensitizer Effects in Colorectal Cancer Cells
DC Field | Value | Language |
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dc.contributor.author | Kwon, Jin-Hee | - |
dc.contributor.author | Lee, Na-Gyeong | - |
dc.contributor.author | Kang, A-Ram | - |
dc.contributor.author | Ahn, In-Ho | - |
dc.contributor.author | Choi, In-Young | - |
dc.contributor.author | Song, Jie-Young | - |
dc.contributor.author | Hwang, Sang-Gu | - |
dc.contributor.author | Um, Hong-Duck | - |
dc.contributor.author | Choi, Jong-Ryoo | - |
dc.contributor.author | Kim, Joon | - |
dc.contributor.author | Park, Jong Kuk | - |
dc.date.accessioned | 2022-12-09T08:00:42Z | - |
dc.date.available | 2022-12-09T08:00:42Z | - |
dc.date.created | 2022-12-08 | - |
dc.date.issued | 2022-10 | - |
dc.identifier.issn | 1420-3049 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/146571 | - |
dc.description.abstract | The objective of this study was to determine whether (5S)-5-(4-benzyloxy-3,5-dimethoxy-phenyl)-5,9-dihydro-8H-furo [3',4':6,7] naphtho [2,3-d] [1,3]dioxol-6-one (JNC-1043), which is a novel chemical derivative of beta-apopicropodophyllin, acts as a novel potential anticancer reagent and radiosensitizer in colorectal cancer (CRC) cells. Firstly, we used MTT assays to assess whether JNC-1043 could inhibit the cell proliferation of HCT116 and DLD-1 cells. The IC50 values of these cell lines were calculated as 114.5 and 157 nM, respectively, at 72 h of treatment. Using doses approximating the IC50 values, we tested whether JNC-1043 had a radiosensitizing effect in the CRC cell lines. Clonogenic assays revealed that the dose-enhancement ratios (DER) of HCT116 and DLD-1 cells were 1.53 and 1.25, respectively. Cell-counting assays showed that the combination of JNC-1043 and gamma-ionizing radiation (IR) enhanced cell death. Treatment with JNC-1043 or IR alone induced cell death by 50 similar to 60%, whereas the combination of JNC-1043 and IR increased this cell death by more than 20 similar to 30%. Annexin V-propidium iodide assays showed that the combination of JNC-1043 and IR increased apoptosis by more 30 similar to 40% compared to that induced by JNC-1043 or IR alone. DCFDA- and MitoSOX-based assays revealed that mitochondrial ROS production was enhanced by the combination of JNC-1043 and IR. Finally, we found that suppression of ROS by N-acetylcysteine (NAC) blocked the apoptotic cell death induced by the combination of JNC-1043 and IR. The xenograft model also indicated that the combination of JNC-1043 and IR increased apoptotic cell death in tumor mass. These results collectively suggest that JNC-1043 acts as a radiosensitizer and exerts anticancer effects against CRC cells by promoting apoptosis mediated by mitochondrial ROS. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.subject | DEATH | - |
dc.subject | CYCLE | - |
dc.subject | STATISTICS | - |
dc.subject | PATHWAY | - |
dc.subject | ARREST | - |
dc.subject | ATM | - |
dc.title | JNC-1043, a Novel Podophyllotoxin Derivative, Exerts Anticancer Drug and Radiosensitizer Effects in Colorectal Cancer Cells | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Joon | - |
dc.identifier.doi | 10.3390/molecules27207008 | - |
dc.identifier.scopusid | 2-s2.0-85140891367 | - |
dc.identifier.wosid | 000873368000001 | - |
dc.identifier.bibliographicCitation | MOLECULES, v.27, no.20 | - |
dc.relation.isPartOf | MOLECULES | - |
dc.citation.title | MOLECULES | - |
dc.citation.volume | 27 | - |
dc.citation.number | 20 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | DEATH | - |
dc.subject.keywordPlus | CYCLE | - |
dc.subject.keywordPlus | STATISTICS | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | ARREST | - |
dc.subject.keywordPlus | ATM | - |
dc.subject.keywordAuthor | JNC-1043 | - |
dc.subject.keywordAuthor | radiosensitizer | - |
dc.subject.keywordAuthor | topoisomerase inhibitor | - |
dc.subject.keywordAuthor | ROS | - |
dc.subject.keywordAuthor | apoptosis | - |
dc.subject.keywordAuthor | colorectal cancer | - |
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