Conjugation of doxorubicin to cell penetrating peptides sensitizes human breast MDA-MB 231 cancer cells to endogenous TRAIL-induced apoptosis

Autor: Jacqueline Bréard, Michel De Waard, Jocelyne Hamelin, Souhir Brahim, Abderraouf Kenani, Sonia Aroui
Přispěvatelé: Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes moléculaires et pathologies, Unité 05/UR/09-09-Faculté de Médecine de Monastir [Tunisie], Recepteurs et Signalisation des Interleukines (U749), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ministère de l'enseignement supérieur, de la recherche scientifique et de la technologie (Tunisia) for financial support and the University of Monastir., Faculté de Médecine de Monastir [Tunisie]-Unité 05/UR/09-09, Canepari, Marco
Rok vydání: 2009
Předmět:
Cancer Research
Clinical Biochemistry
Cell
MESH: Membrane Microdomains
Pharmaceutical Science
Apoptosis
TNF-Related Apoptosis-Inducing Ligand
chemistry.chemical_compound
0302 clinical medicine
polycyclic compounds
Cytotoxic T cell
Drug Carriers
0303 health sciences
MESH: Peptides
Combination chemotherapy
MESH: Drug Resistance
Neoplasm
3. Good health
Cell biology
MESH: Drug Carriers
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
MESH: TNF-Related Apoptosis-Inducing Ligand
medicine.drug
Programmed cell death
Ceramide
Breast Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
macromolecular substances
Biology
Ceramides
MESH: Doxorubicin
03 medical and health sciences
Membrane Microdomains
[SDV.CAN] Life Sciences [q-bio]/Cancer
medicine
Humans
Doxorubicin
MESH: Receptors
TNF-Related Apoptosis-Inducing Ligand
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
030304 developmental biology
Pharmacology
MESH: Humans
MESH: Apoptosis
organic chemicals
Biochemistry (medical)
technology
industry
and agriculture
Cell Biology
MESH: Ceramides
carbohydrates (lipids)
Receptors
TNF-Related Apoptosis-Inducing Ligand
chemistry
Drug Resistance
Neoplasm
Cancer cell
Peptides
MESH: Female
MESH: Breast Neoplasms
Zdroj: Apoptosis
Apoptosis, Springer Verlag, 2009, 14 (11), pp.1352-65. ⟨10.1007/s10495-009-0397-8⟩
Apoptosis, 2009, 14 (11), pp.1352-65. ⟨10.1007/s10495-009-0397-8⟩
ISSN: 1573-675X
1360-8185
DOI: 10.1007/s10495-009-0397-8
Popis: International audience; Previous work from our laboratory has shown that coupling doxorubicin (Dox) to cell penetrating peptides (Dox-CPPs) is a good strategy to overcome Dox resistance in MDA-MB 231 breast cancer cells. We also reported that, in contrast to unconjugated Dox-induced cell death, the increase in apoptotic response does not involve the mitochondrial apoptotic pathway. In this study, we demonstrate that both Dox and Dox-CPPs can increase the density of the TRAIL receptors DR4 and DR5 at the plasma membrane and moderately sensitize MDA-MB 231 cells to exogeneously added recombinant TRAIL, as has already been shown for other chemotherapeutic drugs. Moreover, we show that Dox-CPPs, used alone, induce the clustering of TRAIL receptors into ceramide-enriched membrane lipid rafts, a property not shared by unconjugated Dox and that this process is due to the generation of ceramide during Dox-CPPs treatment. In addition, MDA-MB 231 cells were found to express TRAIL and we show that the increased apoptotic rate induced by Dox-CPPs is due to the sensitization of MDA-MB 231 cells to endogenous TRAIL. The capacity of Dox-CPPs to sensitize cancer cells to physiologic amounts of TRAIL suggests that, in addition to their efficiency in combination chemotherapy, these compounds might increase the response of tumor cells to cytotoxic lymphocyte-mediated killing via TRAIL.
Databáze: OpenAIRE
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