title: Probenecid is a chemosensitizer in cancer cell lines.
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.
authors.affiliation: Cancer Functional Genomics Laboratory, National Institute of Genomic Medicine, Periferico Sur 4124, 01900 Mexico City, Mexico. cadenise79@gmail.com
authors.forename: Denise
authors.initials: D
authors.lastname: Campos-Arroyo
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Martínez-Lazcano
authors.forename: Jorge
authors.initials: J
authors.lastname: Melendez-Zajgla
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D011339:Probenecid / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
chemical_list: D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; D017239:Paclitaxel; D011339:Probenecid; D002945:Cisplatin