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Cytotoxicity, intracellular distribution and uptake of doxorubicin and doxorubicin coupled to cell-penetrating peptides in different cell lines: a comparative study.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2010 Jan 01; Vol. 391 (1), pp. 419-25. Date of Electronic Publication: 2009 Nov 13. - Publication Year :
- 2010
-
Abstract
- 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.<br /> (Copyright 2009 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibiotics, Antineoplastic chemistry
Biological Transport
CHO Cells
Carrier Proteins chemistry
Cell Line, Tumor
Cell-Penetrating Peptides
Cricetinae
Cricetulus
Doxorubicin chemistry
Humans
Peptide Fragments chemistry
tat Gene Products, Human Immunodeficiency Virus chemistry
Antibiotics, Antineoplastic metabolism
Antibiotics, Antineoplastic pharmacology
Carrier Proteins metabolism
Doxorubicin metabolism
Doxorubicin pharmacology
Peptide Fragments metabolism
tat Gene Products, Human Immunodeficiency Virus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 391
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 19914216
- Full Text :
- https://doi.org/10.1016/j.bbrc.2009.11.073