Enantiopure titanocene complexes: direct evidence for paraptosis in cancer cells
Tolerated by normal tissues, anti-cancer therapies based on titanium compounds are limited by low efficacy/selectivity and lack of understanding of their mode(s) of action. In vitro antitumour activity and mode of cell death incurred by enantiopure TiCl2{n-C5H4CHEt(2 MeOPh)}2 (abbreviated CpR 2TiCl2...
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| Format: | Article |
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Royal Society of Chemistry
2016
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| Online Access: | https://eprints.nottingham.ac.uk/31374/ |
| _version_ | 1848794186799644672 |
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| author | Cini, Melchior Williams, Huw Edward Llewelyn Fay, Mike W. Searle, Mark Woodward, Simon Bradshaw, Tracey D. |
| author_facet | Cini, Melchior Williams, Huw Edward Llewelyn Fay, Mike W. Searle, Mark Woodward, Simon Bradshaw, Tracey D. |
| author_sort | Cini, Melchior |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Tolerated by normal tissues, anti-cancer therapies based on titanium compounds are limited by low efficacy/selectivity and lack of understanding of their mode(s) of action. In vitro antitumour activity and mode of cell death incurred by enantiopure TiCl2{n-C5H4CHEt(2 MeOPh)}2 (abbreviated CpR 2TiCl2) has been investigated. The in vitro anti-tumour activity of CpR 2TiCl2 is selective for cancer cells; in clonogenic assays, (S,S)-CpR 2TiCl2 was twice as effective at inhibiting colony formation than other stereoisomers after 24 h exposure. HPLC, MS and NMR techniques determined hydrolysis of CpR 2TiCl2; data strongly correlate with soluble [CpR 2Ti(OH (OH2)]+ being the biological trigger. Treatment of cells with CpR 2TiCl2 provoked extensive cytoplasmic vacuolization, endoplasmic reticulum (ER) swelling and activation of MAPKinase signal transduction, consistent with ligand-induced paraptosis, type III cell death, which is morphologically distinct from, and independent of apoptosis. Indeed, distinct from cisplatin, CpR 2TiCl2 failed to perturb cell cycle dynamics, induce γH2AX foci or evoke apoptosis in MDA-MB-468 and HCT-116 cells. |
| first_indexed | 2025-11-14T19:12:12Z |
| format | Article |
| id | nottingham-31374 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:12:12Z |
| publishDate | 2016 |
| publisher | Royal Society of Chemistry |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-313742020-05-04T17:31:37Z https://eprints.nottingham.ac.uk/31374/ Enantiopure titanocene complexes: direct evidence for paraptosis in cancer cells Cini, Melchior Williams, Huw Edward Llewelyn Fay, Mike W. Searle, Mark Woodward, Simon Bradshaw, Tracey D. Tolerated by normal tissues, anti-cancer therapies based on titanium compounds are limited by low efficacy/selectivity and lack of understanding of their mode(s) of action. In vitro antitumour activity and mode of cell death incurred by enantiopure TiCl2{n-C5H4CHEt(2 MeOPh)}2 (abbreviated CpR 2TiCl2) has been investigated. The in vitro anti-tumour activity of CpR 2TiCl2 is selective for cancer cells; in clonogenic assays, (S,S)-CpR 2TiCl2 was twice as effective at inhibiting colony formation than other stereoisomers after 24 h exposure. HPLC, MS and NMR techniques determined hydrolysis of CpR 2TiCl2; data strongly correlate with soluble [CpR 2Ti(OH (OH2)]+ being the biological trigger. Treatment of cells with CpR 2TiCl2 provoked extensive cytoplasmic vacuolization, endoplasmic reticulum (ER) swelling and activation of MAPKinase signal transduction, consistent with ligand-induced paraptosis, type III cell death, which is morphologically distinct from, and independent of apoptosis. Indeed, distinct from cisplatin, CpR 2TiCl2 failed to perturb cell cycle dynamics, induce γH2AX foci or evoke apoptosis in MDA-MB-468 and HCT-116 cells. Royal Society of Chemistry 2016-01-18 Article PeerReviewed Cini, Melchior, Williams, Huw Edward Llewelyn, Fay, Mike W., Searle, Mark, Woodward, Simon and Bradshaw, Tracey D. (2016) Enantiopure titanocene complexes: direct evidence for paraptosis in cancer cells. Metallomics . ISSN 1756-591X Titanocenes chiral cyclopentadienyls paraptosis cancer http://pubs.rsc.org/en/Content/ArticleLanding/2016/MT/C5MT00297D#!divAbstract doi:10.1039/C5MT00297D doi:10.1039/C5MT00297D |
| spellingShingle | Titanocenes chiral cyclopentadienyls paraptosis cancer Cini, Melchior Williams, Huw Edward Llewelyn Fay, Mike W. Searle, Mark Woodward, Simon Bradshaw, Tracey D. Enantiopure titanocene complexes: direct evidence for paraptosis in cancer cells |
| title | Enantiopure titanocene complexes: direct evidence for
paraptosis in cancer cells |
| title_full | Enantiopure titanocene complexes: direct evidence for
paraptosis in cancer cells |
| title_fullStr | Enantiopure titanocene complexes: direct evidence for
paraptosis in cancer cells |
| title_full_unstemmed | Enantiopure titanocene complexes: direct evidence for
paraptosis in cancer cells |
| title_short | Enantiopure titanocene complexes: direct evidence for
paraptosis in cancer cells |
| title_sort | enantiopure titanocene complexes: direct evidence for
paraptosis in cancer cells |
| topic | Titanocenes chiral cyclopentadienyls paraptosis cancer |
| url | https://eprints.nottingham.ac.uk/31374/ https://eprints.nottingham.ac.uk/31374/ https://eprints.nottingham.ac.uk/31374/ |