Antiangiogenic platinum through glycan targeting
-
Altmetric Citations
Peterson, Erica; Daniel, Gerard A; Katner, Samantha; Bohlmann, Lisa; Chang, Chih-Wei; BEZOS, ANNA; Parish, Christopher; von Itzstein, Mark; Berners-Price, Susan J; Farrell, Nicholas P
Description
Heparan sulfate is identified as a ligand receptor for polynuclear platinum anti-cancer agents through sulfate cluster binding. We present a new biological role for platinum and coordination compounds and a new target for metal-based drugs while presenting a new chemotype for heparanase and growth factor inhibition through modulation (metalloshielding) of their interactions. Masking of extracellular (ECM)-resident heparan sulfate (HS) through metalloshielding results in very effective...[Show more]
dc.contributor.author | Peterson, Erica | |
---|---|---|
dc.contributor.author | Daniel, Gerard A | |
dc.contributor.author | Katner, Samantha | |
dc.contributor.author | Bohlmann, Lisa | |
dc.contributor.author | Chang, Chih-Wei | |
dc.contributor.author | BEZOS, ANNA | |
dc.contributor.author | Parish, Christopher | |
dc.contributor.author | von Itzstein, Mark | |
dc.contributor.author | Berners-Price, Susan J | |
dc.contributor.author | Farrell, Nicholas P | |
dc.date.accessioned | 2021-05-10T01:02:08Z | |
dc.date.available | 2021-05-10T01:02:08Z | |
dc.identifier.issn | 2041-6520 | |
dc.identifier.uri | http://hdl.handle.net/1885/232554 | |
dc.description.abstract | Heparan sulfate is identified as a ligand receptor for polynuclear platinum anti-cancer agents through sulfate cluster binding. We present a new biological role for platinum and coordination compounds and a new target for metal-based drugs while presenting a new chemotype for heparanase and growth factor inhibition through modulation (metalloshielding) of their interactions. Masking of extracellular (ECM)-resident heparan sulfate (HS) through metalloshielding results in very effective inhibition of physiologically critical HS functions including enzyme (heparanase, HPSE) and protein growth factor recognition. The interaction of the highly cationic polynuclear platinum complexes (PPCs) with the highly sulfated pentasaccharide Fondaparinux (FPX, in this case as a model HS-like substrate) results in inhibition of its cleavage by the HS-related enzyme heparanase. Binding of the fibroblast growth factor FGF-2 to HS is also inhibited with consequences for downstream signalling events as measured by a reduction in accumulation of phospho-S6 ribosomal protein in human colon tumor HCT-116 cells. The end-point of inhibition of HPSE activity and growth factor growth factor signaling is the prevention of cell invasion and angiogenesis. Finally these events culminate in inhibition of HCT-116 cell invasion at sub-cytotoxic concentrations and the process of angiogenesis. A competition assay shows that Fondaparinux can sequester the 8+ TriplatinNC from bound DNA, emphasising the strength of PPC–HS interactions. Altering the profile of platinum agents from cytotoxic to anti-metastatic has profound implications for future directions in the development of platinum-based chemotherapeutics. | |
dc.description.sponsorship | This work was supported by grants from NIH (RO1CA78754) to NPF and The Australian Research Council (DP150100308) to SBP, MvI and NPF and from the Australian National Health and Medical Research Council (455395) to CRP. Support from The Massey Cancer Center CA016059 is gratefully acknowledged. | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en_AU | |
dc.publisher | Royal Society of Chemistry | |
dc.rights | © The Royal Society of Chemistry 2017 | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/3.0/ | |
dc.source | Chemical Science | |
dc.title | Antiangiogenic platinum through glycan targeting | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 8 | |
dc.date.issued | 2017 | |
local.identifier.absfor | 030402 - Biomolecular Modelling and Design | |
local.identifier.absfor | 111201 - Cancer Cell Biology | |
local.identifier.ariespublication | u4485658xPUB41 | |
local.publisher.url | http://pubs.rsc.org/en/Journals/JournalIssues/SC | |
local.type.status | Published Version | |
local.contributor.affiliation | Peterson, Erica, Virginia Commonwealth University | |
local.contributor.affiliation | Daniel, Gerard A, Virginia Commonwealth University | |
local.contributor.affiliation | Katner, Samantha, Virginia Commonwealth University | |
local.contributor.affiliation | Bohlmann, Lisa, Griffith University | |
local.contributor.affiliation | Chang, Chih-Wei, Griffith University | |
local.contributor.affiliation | Bezos, Anna, College of Health and Medicine, ANU | |
local.contributor.affiliation | Parish, Christopher, College of Health and Medicine, ANU | |
local.contributor.affiliation | von Itzstein, Mark, Griffith University | |
local.contributor.affiliation | Berners-Price, Susan J, Griffith University | |
local.contributor.affiliation | Farrell, Nicholas P, Virginia Commonwealth University | |
dc.relation | http://purl.org/au-research/grants/arc/DP150100308 | |
dc.relation | http://purl.org/au-research/grants/nhmrc/455395 | |
local.bibliographicCitation.issue | 1 | |
local.bibliographicCitation.startpage | 241 | |
local.bibliographicCitation.lastpage | 252 | |
local.identifier.doi | 10.1039/c6sc02515c | |
dc.date.updated | 2020-11-23T10:11:48Z | |
local.identifier.scopusID | 2-s2.0-85007201906 | |
local.identifier.thomsonID | 000391454500026 | |
dcterms.accessRights | Open Access | |
dc.provenance | This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. | |
dc.rights.license | Creative Commons Attribution-NonCommercial 3.0 Unported Licence | |
Collections | ANU Research Publications |
Download
File | Description | Size | Format | Image |
---|---|---|---|---|
01_Peterson_Antiangiogenic_platinum_2017.pdf | 1.24 MB | Adobe PDF |
This item is licensed under a Creative Commons License
Updated: 17 November 2022/ Responsible Officer: University Librarian/ Page Contact: Library Systems & Web Coordinator