A comparison of signaling activities induced by taxol and desoxyepothilone B Journal Article
| Authors: | Bergstralh, D. T.; Taxman, D. J.; Chou, T. C.; Danishefsky, S. J.; Ting, J. P. Y. |
| Article Title: | A comparison of signaling activities induced by taxol and desoxyepothilone B |
| Abstract: | Desoxyepothilone B (dEpoB), currently in clinical trials, is a novel microtubule inhibitor with similar mode-of-action to paclitaxel (Taxol). Intriguingly, it is effective in some cell lines and tumor xenografts refractory to Taxol. The purpose of this study is to compare signaling induced by the two drugs and identify a molecular basis for increased efficacy of dEpoB in resistant lines. The importance of ERK signaling, already established for Taxol, was shown for dEpoB and other G2-blocking agents. However, a role in differential sensitivity was not observed. Affymetrix analysis shows similar gene modulation by either agent, alone or in combination with MEK inhibitor. Differential sensitivity in a set of Taxol-resistant lines correlated to the expression of P-glycoprotein (P-gp), and its importance was demonstrated directly. These results suggest that Taxol and dEpoB elicit similar cell death pathways, and the increased efficacy of dEpoB in resistant tumor lines lies in differential susceptibility to P-gp. |
| Keywords: | signal transduction; mitogen activated protein kinase; controlled study; protein expression; unclassified drug; human cell; review; drug efficacy; paclitaxel; sensitivity analysis; adenocarcinoma; cell death; mitogen activated protein kinase inhibitor; lung neoplasms; antineoplastic agents, phytogenic; drug resistance, neoplasm; tumor cells, cultured; breast neoplasms; gene expression regulation; correlation analysis; drug mechanism; nucleotide sequence; microtubule assembly; inhibition kinetics; roscovitine; unindexed sequence; mek; p-glycoprotein; epothilones; epothilone derivative; colchicine; drug resistance, multiple; nocodazole; taxol; glycoprotein p; 1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene; mdr; 12,13 desoxyepothilone b; humans; human; female; depob; p-gp; olomoucine |
| Journal Title: | Journal of Chemotherapy |
| Volume: | 16 |
| Issue: | 6 |
| ISSN: | 1120-009X |
| Publisher: | E I F T Srl |
| Date Published: | 2004-12-01 |
| Start Page: | 563 |
| End Page: | 576 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 15700849 |
| DOI: | 10.1179/joc.2004.16.6.563 |
| DOI/URL: | |
| Notes: | J. Chemother. -- Cited By (since 1996):10 -- Export Date: 16 June 2014 -- CODEN: JCHEE C2 - 15700849 -- Molecular Sequence Numbers: GENBANK: AA533071, AA904505, AB011117, AB013382, AB014559, AB028949, AB029011, AF022728, AF022797, AF052178, AF053356, AF054984, AF082559, AF091087, AI400011, AJ001982, AJ222700, AL021977, AL040446, AL079273, AL080169, AL080235, D10495, D50683, D89078, L08246, L21998, L37792, M17017, M23892, M36820, M59371, M69199, R89044, S81914, U09210, U09937, U69611, U70732, U76366, U80457, U89278, X00457, X02419, X70070, X79781, X94553, X96381, Y18207, Z50194; -- Source: Scopus |
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