Sponsor
This work was supported by National Institute on Deafness and Other Communication Disorders at the National Institutes of Health (R21 DC010231) and Medical Research Foundation of Oregon grants to P.S.S. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Published In
PLoS ONE
Document Type
Article
Publication Date
6-3-2013
Subjects
Antineoplastic agents -- Side effects -- Chemotherapy, Antineoplastic agents -- Cisplatin -- Toxicology, Antineoplastic agents -- Cisplatin -- Effectiveness, Cancer -- Chemotherapy -- Complications
Abstract
Cisplatin is widely used as an antineoplastic drug, but its ototoxic and nephrotoxic side-effects, as well as the inherent or acquired resistance of some cancers to cisplatin, remain significant clinical problems. Cisplatin’s selectivity in killing rapidly proliferating cancer cells is largely dependent on covalent binding to DNA via cisplatin’s chloride sites that had been aquated. We hypothesized that cisplatin’s toxicity in slowly proliferating or terminally differentiated cells is primarily due to drug-protein interactions, instead of drug-DNA binding. To identify proteins that bind to cisplatin, we synthesized two different platinum-agarose conjugates, one with two amino groups and another with two chlorides attached to platinum that are available for protein binding, and conducted pull-down assays using cochlear and kidney cells. Mass spectrometric analysis on protein bands after gel electrophoresis and Coomassie blue staining identified several proteins, including myosin IIA, glucose-regulated protein 94 (GRP94), heat shock protein 90 (HSP90), calreticulin, valosin containing protein (VCP), and ribosomal protein L5, as cisplatin-binding proteins. Future studies on the interaction of these proteins with cisplatin will elucidate whether these drug-protein interactions are involved in ototoxicity and nephrotoxicity, or contribute to tumor sensitivity or resistance to cisplatin treatment.
DOI
10.1371/journal.pone.0066220
Persistent Identifier
http://archives.pdx.edu/ds/psu/9575
Citation Details
Karasawa, Takatoshi, et al. "Identification of Cisplatin-Binding Proteins Using Agarose Conjugates of Platinum Compounds." PLOS ONE 8.6 (2013): e66220.
Description
Copyright 2013 Karasawa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.