Microtubule-targeting-compound PBOX-15 radiosensitizes cancer cells in vitro.

Hdl Handle:
http://hdl.handle.net/10147/135110
Title:
Microtubule-targeting-compound PBOX-15 radiosensitizes cancer cells in vitro.
Authors:
Forde, James C; Maginn, Elaina N; McNamara, Gillian; Martin, Lynn M; Campiani, Guiseppe; Williams, D Clive; Zisterer, Daniela; McElligott, Anthony M; Lawler, Mark; Lynch, Thomas H; Hollywood, Donal; Marignol, Laure
Affiliation:
Prostate Molecular Oncology Research Group, Academic Unit of Clinical and Molecular Oncology, St James's Hospital and Trinity College Dublin, Ireland.
Citation:
Microtubule-targeting-compound PBOX-15 radiosensitizes cancer cells in vitro. 2011, 11 (4):421-8 Cancer Biol. Ther.
Journal:
Cancer biology & therapy
Issue Date:
15-Feb-2011
URI:
http://hdl.handle.net/10147/135110
PubMed ID:
21131779
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/21131779
Abstract:
We proposed to investigate the radiosensitizing properties of PBOX-15, a novel microtubule-disrupting agent, in a panel of cancer cell lines.; PBOX-15 treatment was associated with significant cell kill and increased radiosensitivity in all three cell lines tested. The number of surviving cells in response to the combined treatment was significantly less than PBOX -15 alone in 22Rv1 cells. In these cells, radiosensitisation correlated with induction of G2/M cell cycle arrest by PBOX-15. The compound sustained its activity and increased HIF-1Α expression under hypoxic conditions. PBOX-15 prevented onset of hypoxia-induced radioresistance in hypoxic prostate cells and reduced the surviving fraction of irradiated hypoxic cells to levels similar to those achieved under aerobic conditions.; Clonogenic assays were used to determine sensitivity of a panel of cancer cell lines (22Rv1, A549, U87) to PBOX-15 alone or in combination with a single 2Gy dose fraction. Induction of cell cycle arrest and apoptosis was investigated in 22Rv1 prostate cancer cells. The cytotoxic properties of the compound under hypoxic conditions were correlated with Hypoxia Inducible Factor 1 alpha (HIF-1Α) gene and protein expression levels and its radiosensitisation potential was investigated in hypoxic 22Rv1 using clonogenic assays.; This preliminary data identifies the potential of PBOX-15 as a novel radiosensitising agent for the management of solid tumours and eradication of hypoxic cells.
Item Type:
Article
Language:
en
MeSH:
Aerobiosis; Anoxia; Apoptosis; Cell Cycle; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Microtubules; Neoplasms; Oxazepines; Pyrroles; Radiation Tolerance; Radiation-Sensitizing Agents
ISSN:
1555-8576

Full metadata record

DC FieldValue Language
dc.contributor.authorForde, James Cen
dc.contributor.authorMaginn, Elaina Nen
dc.contributor.authorMcNamara, Gillianen
dc.contributor.authorMartin, Lynn Men
dc.contributor.authorCampiani, Guiseppeen
dc.contributor.authorWilliams, D Cliveen
dc.contributor.authorZisterer, Danielaen
dc.contributor.authorMcElligott, Anthony Men
dc.contributor.authorLawler, Marken
dc.contributor.authorLynch, Thomas Hen
dc.contributor.authorHollywood, Donalen
dc.contributor.authorMarignol, Laureen
dc.date.accessioned2011-07-01T15:28:53Z-
dc.date.available2011-07-01T15:28:53Z-
dc.date.issued2011-02-15-
dc.identifier.citationMicrotubule-targeting-compound PBOX-15 radiosensitizes cancer cells in vitro. 2011, 11 (4):421-8 Cancer Biol. Ther.en
dc.identifier.issn1555-8576-
dc.identifier.pmid21131779-
dc.identifier.urihttp://hdl.handle.net/10147/135110-
dc.description.abstractWe proposed to investigate the radiosensitizing properties of PBOX-15, a novel microtubule-disrupting agent, in a panel of cancer cell lines.-
dc.description.abstractPBOX-15 treatment was associated with significant cell kill and increased radiosensitivity in all three cell lines tested. The number of surviving cells in response to the combined treatment was significantly less than PBOX -15 alone in 22Rv1 cells. In these cells, radiosensitisation correlated with induction of G2/M cell cycle arrest by PBOX-15. The compound sustained its activity and increased HIF-1Α expression under hypoxic conditions. PBOX-15 prevented onset of hypoxia-induced radioresistance in hypoxic prostate cells and reduced the surviving fraction of irradiated hypoxic cells to levels similar to those achieved under aerobic conditions.-
dc.description.abstractClonogenic assays were used to determine sensitivity of a panel of cancer cell lines (22Rv1, A549, U87) to PBOX-15 alone or in combination with a single 2Gy dose fraction. Induction of cell cycle arrest and apoptosis was investigated in 22Rv1 prostate cancer cells. The cytotoxic properties of the compound under hypoxic conditions were correlated with Hypoxia Inducible Factor 1 alpha (HIF-1Α) gene and protein expression levels and its radiosensitisation potential was investigated in hypoxic 22Rv1 using clonogenic assays.-
dc.description.abstractThis preliminary data identifies the potential of PBOX-15 as a novel radiosensitising agent for the management of solid tumours and eradication of hypoxic cells.-
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/21131779en
dc.subject.meshAerobiosis-
dc.subject.meshAnoxia-
dc.subject.meshApoptosis-
dc.subject.meshCell Cycle-
dc.subject.meshCell Line, Tumor-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshHumans-
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subunit-
dc.subject.meshMale-
dc.subject.meshMicrotubules-
dc.subject.meshNeoplasms-
dc.subject.meshOxazepines-
dc.subject.meshPyrroles-
dc.subject.meshRadiation Tolerance-
dc.subject.meshRadiation-Sensitizing Agents-
dc.titleMicrotubule-targeting-compound PBOX-15 radiosensitizes cancer cells in vitro.en
dc.typeArticleen
dc.contributor.departmentProstate Molecular Oncology Research Group, Academic Unit of Clinical and Molecular Oncology, St James's Hospital and Trinity College Dublin, Ireland.en
dc.identifier.journalCancer biology & therapyen
dc.description.provinceLeinster-

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