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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 2/2012

01-02-2012 | Original Article

Probenecid is a chemosensitizer in cancer cell lines

Authors: Denise Campos-Arroyo, Juan Carlos Martínez-Lazcano, Jorge Melendez-Zajgla

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2012

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Abstract

Resistance and toxicity are the major barriers to successful cancer chemotherapies. Developing molecules that reduce drug resistance and improve antineoplastic effects is of great interest for cancer research; ideally, these substances should not affect the pharmacodynamics of the chemotherapeutic agent while providing a synergistic antineoplastic effect. In this study, we tested in vitro co-administration of the antineoplastic agents cisplatin or paclitaxel with probenecid, an anion channel inhibitor, in a panel of cancer cell lines to determine the cytotoxicity and synergistic effects of these drug combinations. In addition, we measured the clonogenicity and apoptotic index in these cells. We observed a synergistic interaction between probenecid and the chemotherapeutic agents, and increasing doses of probenecid resulted in a significant decrease in the effective doses of the chemotherapeutic agents. For the antineoplastic agent and probenecid combinations, we found increased cell death, reduced colony formation, and a higher number of apoptotic cells, compared with treatment of cisplatin or paclitaxel alone. Further research is necessary to elucidate the molecular mechanisms by which the synergistic effect occurs. If these synergistic effects can be reproduced in vivo, the co-administration of probenecid with different chemotherapeutic agents may provide a valid treatment in patients with chemotherapy resistance.
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Metadata
Title
Probenecid is a chemosensitizer in cancer cell lines
Authors
Denise Campos-Arroyo
Juan Carlos Martínez-Lazcano
Jorge Melendez-Zajgla
Publication date
01-02-2012
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 2/2012
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-011-1725-6

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