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Targeting telomerase with radiolabeled inhibitors
The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Editions Scientifiques Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154340/ https://www.ncbi.nlm.nih.gov/pubmed/27657809 http://dx.doi.org/10.1016/j.ejmech.2016.09.028 |
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author | Waghorn, Philip A. Jackson, Mark R. Gouverneur, Veronique Vallis, Katherine A. |
author_facet | Waghorn, Philip A. Jackson, Mark R. Gouverneur, Veronique Vallis, Katherine A. |
author_sort | Waghorn, Philip A. |
collection | PubMed |
description | The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells, (123)I-radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An (123)I-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC(50) of 1.58 μM (MST-312 IC(50): 0.23 μM). Clonogenic assays showed a dose dependant effect of (123)I-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435. |
format | Online Article Text |
id | pubmed-5154340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Editions Scientifiques Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-51543402017-01-05 Targeting telomerase with radiolabeled inhibitors Waghorn, Philip A. Jackson, Mark R. Gouverneur, Veronique Vallis, Katherine A. Eur J Med Chem Research Paper The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells, (123)I-radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An (123)I-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC(50) of 1.58 μM (MST-312 IC(50): 0.23 μM). Clonogenic assays showed a dose dependant effect of (123)I-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435. Editions Scientifiques Elsevier 2017-01-05 /pmc/articles/PMC5154340/ /pubmed/27657809 http://dx.doi.org/10.1016/j.ejmech.2016.09.028 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Paper Waghorn, Philip A. Jackson, Mark R. Gouverneur, Veronique Vallis, Katherine A. Targeting telomerase with radiolabeled inhibitors |
title | Targeting telomerase with radiolabeled inhibitors |
title_full | Targeting telomerase with radiolabeled inhibitors |
title_fullStr | Targeting telomerase with radiolabeled inhibitors |
title_full_unstemmed | Targeting telomerase with radiolabeled inhibitors |
title_short | Targeting telomerase with radiolabeled inhibitors |
title_sort | targeting telomerase with radiolabeled inhibitors |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154340/ https://www.ncbi.nlm.nih.gov/pubmed/27657809 http://dx.doi.org/10.1016/j.ejmech.2016.09.028 |
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