Study of Apoptosis Induction and Deoxycytidine Kinase/Cytidine Deaminase Modulation in the Synergistic Interaction of a Novel Ceramide Analog and Gemcitabine in Pancreatic Cancer Cells

This study investigated the interaction between the novel ceramide analog AL6 and gemcitabine in MIA PaCa-2 and PANC-1 pancreatic cancer cell lines, harboring different polymorphic variants of the gemcitabine catabolism enzyme cytidine deaminase (CDA). AL6 dose-dependently inhibited cell growth, ind...

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Bibliographic Details
Published in:Nucleosides, nucleotides & nucleic acids nucleotides & nucleic acids, 2010-06, Vol.29 (4-6), p.419-426
Main Authors: Giovannetti, E., Leon, L. G., Bertini, S., Macchia, M., Minutolo, F., Funel, N., Alecci, C., Giancola, F., Danesi, R., Peters, G. J.
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Cell Line, Tumor
Ceramide analogs
Ceramides - chemistry
Ceramides - pharmacology
cytidine deaminase
Cytidine Deaminase - metabolism
Deoxycytidine - analogs & derivatives
Deoxycytidine - pharmacology
Deoxycytidine Kinase - metabolism
Drug Synergism
Enzyme Activation - drug effects
gemcitabine
Humans
pancreas cancer
Pancreatic Neoplasms - enzymology
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Summary:This study investigated the interaction between the novel ceramide analog AL6 and gemcitabine in MIA PaCa-2 and PANC-1 pancreatic cancer cell lines, harboring different polymorphic variants of the gemcitabine catabolism enzyme cytidine deaminase (CDA). AL6 dose-dependently inhibited cell growth, induced apoptosis and synergistically enhanced the cytotoxic activity of gemcitabine. Moreover, it triggered apoptosis, which was significantly enhanced by the combination, and increased the ratio between gene expression of the activating enzyme deoxycytidine kinase (dCK) and CDA, potentially favoring gemcitabine activity. In conclusion, AL6 displays synergistic cytotoxic activity, enhances apoptosis, and favorably modulates enzymes involved in gemcitabine metabolism, supporting future investigation of this combination in pancreatic cancer.
ISSN:1525-7770
1532-2335
DOI:10.1080/15257771003730193