Effects of a novel carbocyclic analog of pyrrolo[2,3-d]pyrimidine nucleoside on pleiotropic induction of cell death in prostate cancer cells with different androgen responsiveness
DC Field | Value | Language |
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dc.contributor.author | Suh, Hyewon | - |
dc.contributor.author | Choi, Ko-woon | - |
dc.contributor.author | Lee, Jongbok | - |
dc.contributor.author | Ryou, Chongsuk | - |
dc.contributor.author | Rhee, Hakjune | - |
dc.contributor.author | Lee, Chul-Hoon | - |
dc.date.accessioned | 2021-06-22T17:21:50Z | - |
dc.date.available | 2021-06-22T17:21:50Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2016-02 | - |
dc.identifier.issn | 0960-894X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/14527 | - |
dc.description.abstract | Prostate cancer is the most frequently diagnosed cancer and is one of the leading causes of male cancer death in the world. Recently, in the course of our screening for a novel anticancer compound, we synthesized carbocyclic analogs of pyrrolo[2,3-d] pyrimidine nucleoside; compounds 5, and 6. In the current study, we report the effects of compound 5 on pleiotropic induction of cell death via up-regulation of AR-associated p21(Cip1) protein in prostate cancer cells with different androgen responsiveness, such as LNCaP (androgen-dependent and -sensitive), LNCaPC4-2 (androgen-independent and -sensitive; androgen-refractory), and DU145 (androgen-independent and -insensitive) cells. The treatment of LNCaP cells with 6 mu M compound 5 for 24 h stimulated the androgen receptor (AR) activity and dramatically up-regulated transcription (56-fold) of p21(Cip1), which, in turn, induces typical apoptosis in the cells. However, induction of apoptosis through up-regulation (23-fold) of AR-associated p21(Cip1) achieved in LNCaPC4-2 cells was possible by intensive cell treatment with compound 5 (9 mu M, 48 h), because the cells are less sensitive and independent to androgen than LNCaP cells. Furthermore, 6 mu M compound 5-treated DU145 cells, which exhibit extremely low AR activation due to no androgen responsiveness and dependency, showed neither up-regulation of p21(Cip1) nor apoptotic induction. Instead, a different type of cell death, autophagy-like death through the LC3B-associated autophagosome formation, was obviously induced in DU145 cells. Taken together, our results suggest that pleiotropic induction of prostate cancer cell death by compound 5 is determined by how efficiently and how abundantly androgen-dependent activation of the AR occurs, whereas compound 6 shows no induction of apoptosis in LNCaP cells. (C) 2016 Elsevier Ltd. All rights reserved. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | Pergamon Press Ltd. | - |
dc.title | Effects of a novel carbocyclic analog of pyrrolo[2,3-d]pyrimidine nucleoside on pleiotropic induction of cell death in prostate cancer cells with different androgen responsiveness | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Ryou, Chongsuk | - |
dc.contributor.affiliatedAuthor | Rhee, Hakjune | - |
dc.contributor.affiliatedAuthor | Lee, Chul-Hoon | - |
dc.identifier.doi | 10.1016/j.bmcl.2016.01.057 | - |
dc.identifier.scopusid | 2-s2.0-85020367494 | - |
dc.identifier.wosid | 000369377700004 | - |
dc.identifier.bibliographicCitation | Bioorganic and Medicinal Chemistry Letters, v.26, no.4, pp.1130 - 1135 | - |
dc.relation.isPartOf | Bioorganic and Medicinal Chemistry Letters | - |
dc.citation.title | Bioorganic and Medicinal Chemistry Letters | - |
dc.citation.volume | 26 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 1130 | - |
dc.citation.endPage | 1135 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Organic | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | AUTOPHAGY | - |
dc.subject.keywordPlus | SANGIVAMYCIN | - |
dc.subject.keywordPlus | PATHWAYS | - |
dc.subject.keywordPlus | MODEL | - |
dc.subject.keywordAuthor | Pyrrolo[2,3-d]pyrimidine | - |
dc.subject.keywordAuthor | Prostate cancer | - |
dc.subject.keywordAuthor | Apoptosis | - |
dc.subject.keywordAuthor | Autophagy | - |
dc.subject.keywordAuthor | p21(Cip1) | - |
dc.subject.keywordAuthor | Androgen | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0960894X16300579?via%3Dihub | - |
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