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dc.contributor.author
Yacoub, Adly
dc.contributor.author
Han, Song Iy
dc.contributor.author
Caron, Ruben Walter
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dc.contributor.author
Gilfor, Donna
dc.contributor.author
Mooberry, Susan
dc.contributor.author
Grant, Steven
dc.contributor.author
Dent, Paul
dc.date.available
2021-03-12T13:25:43Z
dc.date.issued
2003-11
dc.identifier.citation
Yacoub, Adly; Han, Song Iy; Caron, Ruben Walter; Gilfor, Donna; Mooberry, Susan; et al.; Sequence dependent exposure of mammary carcinoma cells to Taxotere® and the MEK1/2 inhibitor U0126 causes enhanced cell killing in vitro; Taylor & Francis; Cancer Biology & Therapy; 2; 6; 11-2003; 670-676
dc.identifier.issn
1538-4047
dc.identifier.uri
http://hdl.handle.net/11336/128191
dc.description.abstract
Taxol (paclitaxel) and Taxotere (docetaxel) are considered as two of the most important anticancer chemotherapy drugs. The cytotoxic action of these drugs has been linked to their ability to inhibit microtubule depolymerization, causing growth arrest and subsequent cell death. Studies by a number of laboratories have also linked suppression of mitogen activated protein kinase (MAPK) signaling to enhanced Taxol toxicity. The present study examined the interactions of the semi-synthetic taxane Taxotere with MEK1/2 inhibitors in epithelial tumor cells. Concurrent treatment of MDA-MB-231 mammary and DU145 prostate carcinoma cells with Taxotere and MEK1/2 inhibitor resulted in protection from the anti-proliferative effects of Taxotere in MTT assays. In contrast, in MCF-7 mammary cells, concurrent Taxotere and MEK1/2 inhibitor treatment weakly enhanced the antiproliferative effects of the taxane. Sequential treatment of MDA-MB-231 and MCF-7 cells with Taxotere followed by MEK1/2 inhibitor also enhanced the anti-proliferative effects of the taxane in MTT assays. However, no enhancement was observed in DU145 or PC-3 cells. Colony formation assays, including isobologram analyses, provided a more definitive demonstration that MCF-7 and MDA-MB-231 cells were sensitized to the toxic effects of Taxotere by U0126. Similar data were observed using Laulimalide, which binds to tubulin at a different site to Taxotere. The enhancement in Taxotere anti-proliferative effects by U0126 correlated with increased cell killing, 48-72h after treatment of cells that was blocked by inhibition of caspase 9, but not caspase 8, function. This observation was associated with prolonged suppression of ERK1/2 and AKT activity, without alteration in either p38 or JNK1/2 activity. Collectively these findings demonstrate that sequential administration of Taxotere followed by MEK1/2 inhibition can lead to increased cell death and loss of reproductive capacity in some, but not all, human tumor cells. ©2003 Landes Bioscience.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Taylor & Francis
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CLONOGENIC
dc.subject
LAULIMALIDE
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MEK1/2 INHIBITOR
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MTT
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SURVIVAL
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TAXANE
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TAXOTERE
dc.subject.classification
Otras Ciencias Médicas
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dc.subject.classification
Otras Ciencias Médicas
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Sequence dependent exposure of mammary carcinoma cells to Taxotere® and the MEK1/2 inhibitor U0126 causes enhanced cell killing in vitro
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-01-18T15:48:24Z
dc.identifier.eissn
1555-8576
dc.journal.volume
2
dc.journal.number
6
dc.journal.pagination
670-676
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Austin
dc.description.fil
Fil: Yacoub, Adly. Virginia Commonwealth University; Estados Unidos
dc.description.fil
Fil: Han, Song Iy. Virginia Commonwealth University; Estados Unidos
dc.description.fil
Fil: Caron, Ruben Walter. Virginia Commonwealth University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
dc.description.fil
Fil: Gilfor, Donna. Virginia Commonwealth University; Estados Unidos
dc.description.fil
Fil: Mooberry, Susan. Southwest Foundation for Biomedical Research; Estados Unidos
dc.description.fil
Fil: Grant, Steven. Virginia Commonwealth University; Estados Unidos
dc.description.fil
Fil: Dent, Paul. Virginia Commonwealth University; Estados Unidos
dc.journal.title
Cancer Biology & Therapy
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/pdf/10.4161/cbt.2.6.534
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.4161/cbt.2.6.534
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