Show item record

dc.contributor.authorFortin, Jessica
dc.contributor.authorCôté, Marie-France
dc.contributor.authorDeschesnes, Réna G.
dc.contributor.authorPatenaude, Alexandre
dc.contributor.authorLacroix, Jacques
dc.contributor.authorBenoit-Biancamano, Marie-Odile
dc.contributor.authorC.-Gaudreault, René
dc.date.accessioned2015-07-13T16:54:28Z
dc.date.availableNO_RESTRICTIONfr
dc.date.available2015-07-13T16:54:28Z
dc.date.issued2014-04
dc.identifier.citationFortin, Jessica S., Côté, Marie-France, Deschesnes, Réna G., Patenaude, Alexandre, Lacroix, Jacques, Benoit-Biancamano, Marie-Odile, C.-Gaudreault, René (2014, April-June). Microtubule disrupting N-phenyl-N’-(2-chloroethyl) ureas display anticancer activity on cell adhesion, P-glycoprotein and BCL-2-mediated drug resistance. International journal of pharmacy and pharmaceutical sciences, 6(2), 171-179.fr
dc.identifier.urihttp://hdl.handle.net/1866/12198
dc.subjectAryl chloroethylureasfr
dc.subjectMitotic agentsfr
dc.subjectResistancefr
dc.subjectMitochondriafr
dc.subjectAnoikisfr
dc.titleMicrotubule disrupting N-phenyl-N’-(2-chloroethyl) ureas display anticancer activity on cell adhesion, P-glycoprotein and BCL-2-mediated drug resistance
dc.typeArticlefr
dc.contributor.affiliationUniversité de Montréal. Faculté de médecine vétérinairefr
UdeM.statutProfesseur(e) / Professorfr
dcterms.abstractObjective: Our research program has focused on the development of promising, soft alkylating N-phenyl-N’-(2-chloroethyl)urea (CEU) compounds which acylate the glutamic acid-198 of β-tubulin, near the binding site of colchicum alkaloids. CEUs inhibit the motility of cancerous cells in vitro and, interestingly, exhibit antiangiogenic and anticancer activity in vivo. Mitotic arrest induced by microtubule-interfering agents such as CEUs remains the major mechanism of their anticancer activity, leading to apoptosis. However, we recently demonstrated that microtubule disruption by CEUs and other common antimicrotubule agents greatly alters the integrity and organization of microtubule-associated structures, the focal adhesion contact, thereby initiating anoikis, an apoptosis-like cell death mechanism caused by the loss of cell contact with the extracellular matrix. Methods: To ascertain the activated signaling pathway profile of CEUs, flow cytometry, Western blot, immunohistochemistry and transfection experiments were performed. Wound-healing and chick embryo assays were carried out to evaluate the antiangiogenic potency of CEUs. Results: CEU-induced apoptosis involved early cell cycle arrest in G2/M and increased level of CDK1/cycline B proteins. These signaling events were followed by the specific activation of the intrinsic apoptosis pathway, involving loss of mitochondrial membrane potential (Δψm) and ROS production, cytochrome c release from mitochondria, caspase activation, AIF nuclear translocation, PARP cleavage and nuclear fragmentation. CEUs maintained their efficacy on cells plated on pro-survival extracellular matrices or exhibiting overexpression of P-glycoprotein or the anti-apoptotic protein Bcl-2. Conclusion: Our results suggest that CEUs represent a promising new class of antimicrotubule, antiangiogenic and pro-anoikis agents.fr
dcterms.bibliographicCitationInternational journal of pharmacy and pharmaceutical sciences ; vol. 6, no 2
dcterms.isPartOfurn:ISSN:0975-1491
dcterms.languageengfr
UdeM.VersionRioxxVersion acceptée / Accepted Manuscript


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show item record