Cytotoxicity, intracellular distribution and uptake of doxorubicin and doxorubicin coupled to cell-penetrating peptides in different cell lines: a comparative study

Autor: Abderraouf Kenani, Michel De Waard, Souhir Brahim, Sonia Aroui
Přispěvatelé: Mécanismes moléculaires et pathologies, Faculté de Médecine de Monastir [Tunisie]-Unité 05/UR/09-09, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), S.A. acknowledges the support of the Ministère de l'enseignement supérieur, de la recherche scientifique et de la technologie (Tunisia) and the University of Monastir for financial support., Canepari, Marco
Rok vydání: 2009
Předmět:
Cell
MESH: Cricetinae
Cell-Penetrating Peptides
Cell-penetrating peptide
Biochemistry
0302 clinical medicine
MESH: Cricetulus
Cricetinae
MESH: Animals
Cytotoxicity
MESH: Peptide Fragments
0303 health sciences
Antibiotics
Antineoplastic
Chinese hamster ovary cell
3. Good health
Drug delivery systems
medicine.anatomical_structure
Cell killing
030220 oncology & carcinogenesis
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
tat Gene Products
Human Immunodeficiency Virus
Intracellular
medicine.drug
MESH: Cell Line
Tumor
MESH: Biological Transport
Biophysics
MESH: Carrier Proteins
CHO Cells
Biology
03 medical and health sciences
MESH: Doxorubicin
Cricetulus
MESH: CHO Cells
Cell Line
Tumor
medicine
Animals
Humans
Doxorubicin
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
MESH: Antibiotics
Antineoplastic
Molecular Biology
030304 developmental biology
MESH: tat Gene Products
Human Immunodeficiency Virus
MESH: Humans
Biological Transport
Cell Biology
Molecular biology
Peptide Fragments
Cell culture
Drug resistance
Carrier Proteins
Zdroj: Biochemical and Biophysical Research Communications
Biochemical and Biophysical Research Communications, Elsevier, 2010, 391 (1), pp.419-25. ⟨10.1016/j.bbrc.2009.11.073⟩
ISSN: 1090-2104
0006-291X
DOI: 10.1016/j.bbrc.2009.11.073⟩
Popis: International audience; One of the major obstacles which are opposed to the success of anticancer treatment is the cell resistance that generally develops after administration of commonly used drugs. In this study, we try to overcome the tumour cell resistance of doxorubicin (Dox) by developing a cell-penetrating peptide (CPP)-anticancer drug conjugate in aim to enhance its intracellular delivery and that its therapeutic effects. For this purpose, two cell-penetrating peptides, penetratin (pene) and tat, derived from the HIV-1 TAT protein, were chemically conjugated to Dox. The cytotoxicity, intracellular distribution and uptake were accessed in CHO cells (Chinese Hamster Ovarian carcinoma cells), HUVEC (Human Umbilical Vein Endothelial Cells), differentiated NG108.15 neuronal cell and breast cancer cells MCF7drug-sensitive or MDA-MB 231 drug-resistant cell lines. The conjugates showed different cell killing activity and intracellular distribution pattern by comparison to Dox as assessed respectively by MTT-based colorimetric cellular cytotoxicity assay, confocal fluorescence microscopy and FACS analysis. After treatment with 3 microM with Dox-CPPs for 2h, pene increase the Dox cytotoxicity by 7.19-fold in CHO cells, by 11.53-fold in HUVEC cells and by 4.87-fold in MDA-MB 231 cells. However, cytotoxicity was decreased in NG108.15 cells and MCF7. Our CPPs-Dox conjugate proves the validity of CPPs for the cytoplasmic delivery of therapeutically useful molecules and also a valuable strategy to overcome drug resistance.
Databáze: OpenAIRE
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