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Article: Platinum(II) N-heterocyclic carbene complexes arrest metastatic tumor growth

TitlePlatinum(II) N-heterocyclic carbene complexes arrest metastatic tumor growth
Authors
Keywordsantimetastasis
metabolism
N-heterocyclic carbene
platinum
vimentin
Issue Date2021
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences, 2021, v. 118 n. 17, p. article no. e2025806118 How to Cite?
AbstractVimentin is a cytoskeletal intermediate filament protein that plays pivotal roles in tumor initiation, progression, and metastasis, and its overexpression in aggressive cancers predicted poor prognosis. Herein described is a highly effective antitumor and antimetastatic metal complex [PtII(C^N^N)(NHC2Bu)]PF6 (Pt1a; HC^N^N = 6-phenyl-2,2′-bipyridine; NHC= N-heterocyclic carbene) that engages vimentin via noncovalent binding interactions with a distinct orthogonal structural scaffold. Pt1a displays vimentin-binding affinity with a dissociation constant of 1.06 µM from surface plasmon resonance measurements and fits into a pocket between the coiled coils of the rod domain of vimentin with multiple hydrophobic interactions. It engages vimentin in cellulo, disrupts vimentin cytoskeleton, reduces vimentin expression in tumors, suppresses xenograft growth and metastasis in different mouse models, and is well tolerated, attributable to biotransformation to less toxic and renal-clearable platinum(II) species. Our studies uncovered the practical therapeutic potential of platinum(II)‒NHC complexes as effective targeted chemotherapy for combating metastatic and cisplatin-resistant cancers.
Persistent Identifierhttp://hdl.handle.net/10722/302376
ISSN
2020 Impact Factor: 11.205
2020 SCImago Journal Rankings: 5.011
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorWan, PK-
dc.contributor.authorTong, KC-
dc.contributor.authorLok, CN-
dc.contributor.authorZhang, C-
dc.contributor.authorChang, XY-
dc.contributor.authorSze, KH-
dc.contributor.authorWong, AST-
dc.contributor.authorChe, CM-
dc.date.accessioned2021-09-06T03:31:24Z-
dc.date.available2021-09-06T03:31:24Z-
dc.date.issued2021-
dc.identifier.citationProceedings of the National Academy of Sciences, 2021, v. 118 n. 17, p. article no. e2025806118-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/302376-
dc.description.abstractVimentin is a cytoskeletal intermediate filament protein that plays pivotal roles in tumor initiation, progression, and metastasis, and its overexpression in aggressive cancers predicted poor prognosis. Herein described is a highly effective antitumor and antimetastatic metal complex [PtII(C^N^N)(NHC2Bu)]PF6 (Pt1a; HC^N^N = 6-phenyl-2,2′-bipyridine; NHC= N-heterocyclic carbene) that engages vimentin via noncovalent binding interactions with a distinct orthogonal structural scaffold. Pt1a displays vimentin-binding affinity with a dissociation constant of 1.06 µM from surface plasmon resonance measurements and fits into a pocket between the coiled coils of the rod domain of vimentin with multiple hydrophobic interactions. It engages vimentin in cellulo, disrupts vimentin cytoskeleton, reduces vimentin expression in tumors, suppresses xenograft growth and metastasis in different mouse models, and is well tolerated, attributable to biotransformation to less toxic and renal-clearable platinum(II) species. Our studies uncovered the practical therapeutic potential of platinum(II)‒NHC complexes as effective targeted chemotherapy for combating metastatic and cisplatin-resistant cancers.-
dc.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.subjectantimetastasis-
dc.subjectmetabolism-
dc.subjectN-heterocyclic carbene-
dc.subjectplatinum-
dc.subjectvimentin-
dc.titlePlatinum(II) N-heterocyclic carbene complexes arrest metastatic tumor growth-
dc.typeArticle-
dc.identifier.emailWong, AST: awong1@hku.hk-
dc.identifier.emailChe, CM: chemhead@hku.hk-
dc.identifier.authorityLok, CN=rp00752-
dc.identifier.authoritySze, KH=rp00785-
dc.identifier.authorityWong, AST=rp00805-
dc.identifier.authorityChe, CM=rp00670-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.2025806118-
dc.identifier.pmid33883283-
dc.identifier.pmcidPMC8092596-
dc.identifier.scopuseid_2-s2.0-85105281911-
dc.identifier.hkuros324873-
dc.identifier.volume118-
dc.identifier.issue17-
dc.identifier.spagearticle no. e2025806118-
dc.identifier.epagearticle no. e2025806118-
dc.publisher.placeUnited States-

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