Fluorinated Cpd 5, a pure arylating K-vitamin derivative, inhibits human hepatoma cell growth by inhibiting Cdc25 and activating MAPK
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kar, Siddhartha | - |
dc.contributor.author | Wang, Meifang | - |
dc.contributor.author | Ham, Seung Wook | - |
dc.contributor.author | Carr, Brian I. | - |
dc.date.available | 2019-05-30T06:38:38Z | - |
dc.date.issued | 2006-11 | - |
dc.identifier.issn | 0006-2952 | - |
dc.identifier.issn | 1873-2968 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/24240 | - |
dc.description.abstract | We previously synthesized several K-vitamin derivatives, which are potent growth inhibitors of human tumor cells, including Hep3B human hepatoma cells. Among these, Cpd 5 was the most potent. However, being a quinone derivative, Cpd 5 has the potential for generating toxic reactive oxygen species (ROS). We therefore synthesized a fluorinated derivative of Cpd 5, F-Cpd 5. The calculated reduction potential of F-Cpd 5 was much higher than that for Cpd S and it was not predicted to generate ROS. This was supported by our observation that F-Cpd 5 generated significantly lower ROS than Cpd 5. F-Cpd 5 was three times more potent than Cpd 5 in inhibiting Hep3B cell growth. Interestingly, under identical culture conditions, F-Cpd 5 inhibited mitogen-induced DNA synthesis in normal rat hepatocytes 12-fold less potently than Hep3B cells. F-Cpd 5 was found to induce caspase-3 cleavage and nuclear DNA laddering, evidences for apoptosis. It preferentially inhibited the activities of the cell cycle controlling phosphatases Cdc25A and Cdc25B, by binding to their catalytic cysteines. Consequently, inhibitory tyrosine phosphorylation of the Cdc25 substrate kinases Cdk2 and Cdk4 were induced. F-Cpd 5 also induced phosphorylation of the MAPK proteins ERK1/2, JNK1/2 and p38 in Hep3B cells and the MAPK inhibitors (U0126, JNKI-II, and SB 203580) antagonized its growth inhibition. F-Cpd 5 inhibited the action of cytosolic ERK phosphatase activity, which likely caused the ERK phosphorylation. F-Cpd 5 thus differentially inhibited growth of normal and tumor cells by preferentially inhibiting the actions of Cdc25A and Cdc25B phosphatases and inducing MAPK phosphorylation. (c) 2006 Elsevier Inc. All rights reserved. | - |
dc.format.extent | 11 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.title | Fluorinated Cpd 5, a pure arylating K-vitamin derivative, inhibits human hepatoma cell growth by inhibiting Cdc25 and activating MAPK | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.bcp.2006.07.024 | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL PHARMACOLOGY, v.72, no.10, pp 1217 - 1227 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000242005400003 | - |
dc.identifier.scopusid | 2-s2.0-33750215412 | - |
dc.citation.endPage | 1227 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 1217 | - |
dc.citation.title | BIOCHEMICAL PHARMACOLOGY | - |
dc.citation.volume | 72 | - |
dc.type.docType | Article | - |
dc.publisher.location | 영국 | - |
dc.subject.keywordAuthor | liver cancer | - |
dc.subject.keywordAuthor | protein phosphatase | - |
dc.subject.keywordAuthor | K-vitamin derivative | - |
dc.subject.keywordAuthor | cell cycle inhibition | - |
dc.subject.keywordAuthor | Cdc25 | - |
dc.subject.keywordAuthor | MAPK | - |
dc.subject.keywordPlus | PROTEIN-TYROSINE PHOSPHORYLATION | - |
dc.subject.keywordPlus | ERK PHOSPHORYLATION | - |
dc.subject.keywordPlus | MENADIONE 2-METHYL-1,4-NAPHTHOQUINONE | - |
dc.subject.keywordPlus | PHOSPHATASE INHIBITORS | - |
dc.subject.keywordPlus | CRYSTAL-STRUCTURE | - |
dc.subject.keywordPlus | DNA-DAMAGE | - |
dc.subject.keywordPlus | CYCLE | - |
dc.subject.keywordPlus | POTENT | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | FAMILY | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
84, Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea (06974)02-820-6194
COPYRIGHT 2019 Chung-Ang University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.