Doxorubicin resistant neuroblastoma cells secrete factors that activate AKT and attenuate cytotoxicity in drug-sensitive cells

The present study aims to verify the hypothesis that tumor cells with acquired resistance to chemotherapy may secrete survival factors and thus, participate in the protection of drug-sensitive cells against drug toxicity. A human neuroblastoma cell line, SK-N-SH, and its doxorubicin resistant deriva...

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Bibliographic Details
Published in:Cancer letters 2002-08, Vol.182 (1), p.53-59
Main Authors: Emran, Mohammad A., Rebbaa, Abdelhadi, Mirkin, Bernard L.
Format: Article
Language:English
Subjects:
Akt
Antibiotics, Antineoplastic - pharmacology
Antineoplastic agents
Apoptosis
Biological and medical sciences
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Caspase 3
Caspases - metabolism
Cell culture
Chemotherapy
Culture Media, Conditioned
Cytotoxicity
Doxorubicin
Doxorubicin - pharmacology
Drug resistance
Drug Resistance, Neoplasm
Glycogen Synthase Kinase 3
Humans
Kinases
Ligands
Medical sciences
Neuroblastoma - drug therapy
Neuroblastoma - metabolism
Pharmacology. Drug treatments
Phosphorylation
Protein-Serine-Threonine Kinases
Proteins
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Survival factors
Toxicity
Tumor Cells, Cultured
Tumors
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Summary:The present study aims to verify the hypothesis that tumor cells with acquired resistance to chemotherapy may secrete survival factors and thus, participate in the protection of drug-sensitive cells against drug toxicity. A human neuroblastoma cell line, SK-N-SH, and its doxorubicin resistant derivative, RDOX6, have been used. Conditioned medium from RDOX6 cells attenuated the cytotoxic response of SK-N-SH cells to doxorubicin. This protective effect was associated with activation of the Akt survival pathway and inhibition of caspase-3. These data indicate that secretion, by drug-resistant cells, of factors that activate anti-apoptotic pathways in drug-sensitive cells, may constitute a novel mechanism of drug resistance.
ISSN:0304-3835
1872-7980
DOI:10.1016/S0304-3835(02)00062-9