Neoamphimedine Circumvents Metnase-Enhanced DNA Topoisomerase II[alpha] Activity Through ATP-Competitive Inhibition
Type IIα DNA topoisomerase (TopoIIα) is among the most important clinical drug targets for the treatment of cancer. Recently, the DNA repair protein Metnase was shown to enhance TopoIIα activity and increase resistance to TopoIIα poisons. Using in vitro DNA decatenation assays we show that neoamphim...
Saved in:
| Published in | Marine drugs Vol. 9; no. 11; p. 2397 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Basel
MDPI AG
01.11.2011
|
| Online Access | Get full text |
Cover
Loading…
| Abstract | Type IIα DNA topoisomerase (TopoIIα) is among the most important clinical drug targets for the treatment of cancer. Recently, the DNA repair protein Metnase was shown to enhance TopoIIα activity and increase resistance to TopoIIα poisons. Using in vitro DNA decatenation assays we show that neoamphimedine potently inhibits TopoIIα-dependent DNA decatenation in the presence of Metnase. Cell proliferation assays demonstrate that neoamphimedine can inhibit Metnase-enhanced cell growth with an IC50 of 0.5 µM. Additionally, we find that the apparent Km of TopoIIα for ATP increases linearly with higher concentrations of neoamphimedine, indicating ATP-competitive inhibition, which is substantiated by molecular modeling. These findings support the continued development of neoamphimedine as an anticancer agent, particularly in solid tumors that over-express Metnase. |
|---|---|
| AbstractList | Type IIα DNA topoisomerase (TopoIIα) is among the most important clinical drug targets for the treatment of cancer. Recently, the DNA repair protein Metnase was shown to enhance TopoIIα activity and increase resistance to TopoIIα poisons. Using in vitro DNA decatenation assays we show that neoamphimedine potently inhibits TopoIIα-dependent DNA decatenation in the presence of Metnase. Cell proliferation assays demonstrate that neoamphimedine can inhibit Metnase-enhanced cell growth with an IC50 of 0.5 µM. Additionally, we find that the apparent Km of TopoIIα for ATP increases linearly with higher concentrations of neoamphimedine, indicating ATP-competitive inhibition, which is substantiated by molecular modeling. These findings support the continued development of neoamphimedine as an anticancer agent, particularly in solid tumors that over-express Metnase. |
| Author | Ashley, Amanda K Amerin, Courtney L Ponder, Jessica Yoo, Byong Hoon Hromas, Robert Reid, Brian G Reigan, Philip Nickoloff, Jac A Abraham, Adedoyin D LaBarbera, Daniel V Li, Qun Zhou, Qiong |
| Author_xml | – sequence: 1 givenname: Jessica surname: Ponder fullname: Ponder, Jessica – sequence: 2 givenname: Byong surname: Yoo middlename: Hoon fullname: Yoo, Byong Hoon – sequence: 3 givenname: Adedoyin surname: Abraham middlename: D fullname: Abraham, Adedoyin D – sequence: 4 givenname: Qun surname: Li fullname: Li, Qun – sequence: 5 givenname: Amanda surname: Ashley middlename: K fullname: Ashley, Amanda K – sequence: 6 givenname: Courtney surname: Amerin middlename: L fullname: Amerin, Courtney L – sequence: 7 givenname: Qiong surname: Zhou fullname: Zhou, Qiong – sequence: 8 givenname: Brian surname: Reid middlename: G fullname: Reid, Brian G – sequence: 9 givenname: Philip surname: Reigan fullname: Reigan, Philip – sequence: 10 givenname: Robert surname: Hromas fullname: Hromas, Robert – sequence: 11 givenname: Jac surname: Nickoloff middlename: A fullname: Nickoloff, Jac A – sequence: 12 givenname: Daniel surname: LaBarbera middlename: V fullname: LaBarbera, Daniel V |
| BookMark | eNqNjrFOwzAURS0EEi0w8AeWmAM2pmk8RqGIDlQM2aqqMskDu6rfM7ZTib_HAx_AdK_uOcOds3MkBMZupbhXSosHP2opH5VenrGZrGtRlXV5yeYpHYRQi0Y_zVjaABkfrPMwOgTeuThM_gSYE3-DjCZBtUJrcICRP29a3lMgl8hDLIiv11tzDNbseDtkd3L5h_c20vRledu_Vx35ANkVUlS07qNUwmt28WmOCW7-8ordvaz67rUKkb4nSHl_oCliQXu5UHXTNLr8_Z_1C-DVUTQ |
| ContentType | Journal Article |
| Copyright | Copyright MDPI AG 2011 |
| Copyright_xml | – notice: Copyright MDPI AG 2011 |
| DBID | 3V. 7T7 7TN 7X7 7XB 88E 8FD 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AZQEC BBNVY BENPR BHPHI BKSAR C1K CCPQU DWQXO F1W FR3 FYUFA GHDGH GNUQQ H95 H99 HCIFZ K9. L.F L.G LK8 M0S M1P M7P P64 PCBAR PIMPY PQEST PQQKQ PQUKI PRINS |
| DOI | 10.3390/md9112397 |
| DatabaseName | ProQuest Central (Corporate) Industrial and Applied Microbiology Abstracts (Microbiology A) Oceanic Abstracts Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) Technology Research Database ProQuest SciTech Collection ProQuest Natural Science Collection Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central ProQuest Central Essentials Biological Science Collection AUTh Library subscriptions: ProQuest Central Natural Science Collection Earth, Atmospheric & Aquatic Science Collection Environmental Sciences and Pollution Management ProQuest One Community College ProQuest Central Korea ASFA: Aquatic Sciences and Fisheries Abstracts Engineering Research Database Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources ASFA: Marine Biotechnology Abstracts SciTech Premium Collection ProQuest Health & Medical Complete (Alumni) Aquatic Science & Fisheries Abstracts (ASFA) Marine Biotechnology Abstracts Aquatic Science & Fisheries Abstracts (ASFA) Professional ProQuest Biological Science Collection Health & Medical Collection (Alumni Edition) Medical Database Biological Science Database Biotechnology and BioEngineering Abstracts Earth, Atmospheric & Aquatic Science Database Publicly Available Content Database ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China |
| DatabaseTitle | Publicly Available Content Database Aquatic Science & Fisheries Abstracts (ASFA) Professional ProQuest Central Student Technology Research Database ProQuest Central Essentials ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest Natural Science Collection ProQuest Central China Environmental Sciences and Pollution Management ProQuest Central Earth, Atmospheric & Aquatic Science Collection Health Research Premium Collection Oceanic Abstracts Health and Medicine Complete (Alumni Edition) Natural Science Collection ProQuest Central Korea Biological Science Collection Aquatic Science & Fisheries Abstracts (ASFA) Marine Biotechnology Abstracts Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources Industrial and Applied Microbiology Abstracts (Microbiology A) ProQuest Medical Library (Alumni) ProQuest Biological Science Collection ProQuest One Academic Eastern Edition Earth, Atmospheric & Aquatic Science Database ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database ProQuest SciTech Collection ProQuest Hospital Collection (Alumni) Biotechnology and BioEngineering Abstracts ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ASFA: Aquatic Sciences and Fisheries Abstracts Engineering Research Database ProQuest One Academic ProQuest Central (Alumni) |
| DatabaseTitleList | Publicly Available Content Database |
| Database_xml | – sequence: 1 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Pharmacy, Therapeutics, & Pharmacology |
| EISSN | 1660-3397 |
| ExternalDocumentID | 3337059191 |
| GroupedDBID | --- 29M 2WC 3V. 53G 5GY 5VS 7T7 7TN 7X7 7XB 88E 8CJ 8FD 8FE 8FH 8FI 8FJ 8FK AADQD AAHBH ABUWG ACGFO ACIHN ACPRK ADBBV ADRAZ AEAQA AENEX AFKRA AFRAH AFZYC AHMBA ALIPV ALMA_UNASSIGNED_HOLDINGS AOIJS AZQEC BAWUL BBNVY BCNDV BENPR BHPHI BKSAR BPHCQ BVXVI C1K CCPQU CS3 D1J DIK DU5 DWQXO E3Z EBD EDH F1W F5P FR3 FYUFA GNUQQ GROUPED_DOAJ GX1 H95 H99 HCIFZ HH5 HMCUK HYE IPNFZ K9. KQ8 L.F L.G LK5 LK8 M1P M48 M7P M7R MK0 MODMG M~E O5R O5S OK1 P2P P64 PCBAR PGMZT PIMPY PQEST PQQKQ PQUKI PRINS PROAC PSQYO RIG RNS RPM TR2 UKHRP XSB |
| ID | FETCH-proquest_journals_15368889003 |
| IEDL.DBID | BENPR |
| IngestDate | Fri Sep 13 01:07:27 EDT 2024 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 11 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-proquest_journals_15368889003 |
| OpenAccessLink | https://www.proquest.com/docview/1536888900/abstract/?pq-origsite=%requestingapplication% |
| PQID | 1536888900 |
| PQPubID | 2032365 |
| ParticipantIDs | proquest_journals_1536888900 |
| PublicationCentury | 2000 |
| PublicationDate | 20111101 |
| PublicationDateYYYYMMDD | 2011-11-01 |
| PublicationDate_xml | – month: 11 year: 2011 text: 20111101 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | Basel |
| PublicationPlace_xml | – name: Basel |
| PublicationTitle | Marine drugs |
| PublicationYear | 2011 |
| Publisher | MDPI AG |
| Publisher_xml | – name: MDPI AG |
| SSID | ssj0035894 |
| Score | 3.6483817 |
| Snippet | Type IIα DNA topoisomerase (TopoIIα) is among the most important clinical drug targets for the treatment of cancer. Recently, the DNA repair protein Metnase... |
| SourceID | proquest |
| SourceType | Aggregation Database |
| StartPage | 2397 |
| SummonAdditionalLinks | – databaseName: Scholars Portal Journals: Open Access dbid: M48 link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3fS8MwED7mfPFF_Ik_phwoe1pka9OufRApdWMTWvbQwUBktF3KCjPVtQP735ukm0OUPTe0JNfk8t3ddx_AfTQzQ6ZFHRJ34phQmxkk0hJKaGJqXYt1Q70t2ciebw7G9GViTGqw0dhcL2D-L7STelLj5eLh67N8Ehv-USJOAdkFdBc7VhOOdQ_2NapT-aN79CeZoBuWTaumQr-H_zl-lU_pH8Hh-jKITmW9Y6gxfgLNUdVNumxhsCVH5S1s4mjbZ7o8hdxnWSiMkcr8OGfopst49S7rF3P0WMGFfyI9Plcpfnz2HQyyjyzNMxmGyhkOh6-KaPuGTlxJSIjvKdEedIIRcdWFWlUW4ZDP00jVdp3BXb8XuAOymdJ0s5ZTcaiZAujKmOU51HnG2QVgO7EMymJdUmepJRvvSaWXWZh0253QYvYlNHa96Wr342s4UMFXRdprQL1YrtiN8N5FdKts8w3sMKIv priority: 102 providerName: Scholars Portal |
| Title | Neoamphimedine Circumvents Metnase-Enhanced DNA Topoisomerase II[alpha] Activity Through ATP-Competitive Inhibition |
| URI | https://www.proquest.com/docview/1536888900/abstract/ |
| Volume | 9 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1La8JAEB6sXnopfdKHlYUWTy7msXmdSmoVLRhCSUEoRZJ1gzl0Y008-O-7u0nwUPCyl8CGZHZmdh7ffADPycqOmZHomOqUYuIxCydGSjBJbcNxmRObmkQjzwN7-kneF9aiBdMGCyPbKhubqAz1KqcyRz4UmmmLaM3TtGGcyCwALYcvm18s-aNknbUm0ziBjqETWbDtvI6D8KOxyqbleqSaLGSKMF-E-0LLDdNz_tlg5Vgm53BW3wiRX4nwAlqMX0I_rEZK7wcoOiCkigHqo_AwbHp_BUXA8lhIJJNFcs7QKNvS3Y9sYizQnJVcOCk85mtV50dvgY-ifJNnRS5zUQVDs9mXQtt-I59WPBLifYq5B_lRiEfqVq3ai9CMr7NENXhdw9NkHI2muPmkZX0ii-Xh_5k30OY5Z7eAtNS1CKOmxM8SV07fk3Qvqzh1ND12mXcH3WM73R9__ACnKgOrkHtdaJfbHXsULrxMenDiLJxeLaOeCoTFOifuHx58qGg |
| link.rule.ids | 315,786,790,870,12083,21416,24346,27957,27958,31754,33779,43345,43840,74102,74659 |
| linkProvider | ProQuest |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1LS8NAEB60HvQiPvFRdUHpqYtpdvM6SagtjbahhwgFkZKkG5qDm9pND_337m5SexB6DmxIZndmZ-b75gN4SmZ2zMykg9NOmmLqMQsnZkYxzWzTcZkTE0OxkUehPfigbxNrUhfcRA2r3PhE7ahnRapq5M_yZNoyW_MM42Xxg5VqlOqu1hIa-3BACaEK0udM_hIuYrkeraYJEZnayxRfnmyTeM4_v6uDSf8EjutbIPIrs53CHuNn0BpXY6TXbRRtWVGijVpovB0wvT4HEbIillbIVWOcM9TNl-nqWwEXBRqxksvAhHt8rnv76DX0UVQsilwUqv4kGAqCT82w_UJ-WmlHyPdptR7kR2Pc1TdpDSlCAZ_niQZ1XcBjvxd1B3jzSdN6F4rp9p-RS2jwgrMrQEbmWpSlRHFmqasm7imJl1mcOUYndpl3Dc1dK93sfvwAh4NoNJwOg_D9Fo50BVYz95rQKJcrdidDeJncazv9Aqmro38 |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1LS8NAEB60gngRn_iouqD01KVpsnmdJNSWRm3IIUJBpCTbDc3BTe22h_57dzepPQg9BzYkszuzM_N98wE8ZVMnZWbWxbRLKSY-s3Fm5gST3DFdj7mpZSg28ihyhh_kdWyPa_yTqGGVG5-oHfW0pKpG3pEn05HZmm8YnbyGRcQvg-f5D1YKUqrTWstp7MOBjJKGUjNwx3_Jl2V7PqkmC1kyzZfpvjzlpuW7_3ywDiyDEziub4QoqEx4CnuMn0ErrkZKr9so2TKkRBu1ULwdNr0-BxGxMpUWKVSTnDPUKxZ09a1AjAKN2JLLIIX7fKb7_OglClBSzstClKoWJRgKw0_Ntv1CAa10JOT7tHIPCpIY9_StWsOLUMhnRaYBXhfwOOgnvSHefNKk3pFisv1_1iU0eMnZFSAj92zCqKX4s8RT0_eU3Ms0zV2jm3rMv4bmrpVudj9-gENposl7GL3dwpEuxmoSXxMay8WK3clovszutZl-AYNKp6s |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Neoamphimedine+Circumvents+Metnase-Enhanced+DNA+Topoisomerase+II%5Balpha%5D+Activity+Through+ATP-Competitive+Inhibition&rft.jtitle=Marine+drugs&rft.au=Ponder%2C+Jessica&rft.au=Yoo%2C+Byong+Hoon&rft.au=Abraham%2C+Adedoyin+D&rft.au=Li%2C+Qun&rft.date=2011-11-01&rft.pub=MDPI+AG&rft.eissn=1660-3397&rft.volume=9&rft.issue=11&rft.spage=2397&rft_id=info:doi/10.3390%2Fmd9112397&rft.externalDBID=HAS_PDF_LINK&rft.externalDocID=3337059191 |