Identification of cisplatin-binding proteins using agarose conjugates of platinum compounds.
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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3670892?pdf=render |
| _version_ | 1828421292326387712 |
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| author | Takatoshi Karasawa Martha Sibrian-Vazquez Robert M Strongin Peter S Steyger |
| author_facet | Takatoshi Karasawa Martha Sibrian-Vazquez Robert M Strongin Peter S Steyger |
| author_sort | Takatoshi Karasawa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T15:27:41Z |
| format | Article |
| id | doaj.art-5dd41c2e95994295930398c3491e778d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T15:27:41Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5dd41c2e95994295930398c3491e778d2022-12-22T01:43:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6622010.1371/journal.pone.0066220Identification of cisplatin-binding proteins using agarose conjugates of platinum compounds.Takatoshi KarasawaMartha Sibrian-VazquezRobert M StronginPeter S SteygerCisplatin 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.http://europepmc.org/articles/PMC3670892?pdf=render |
| spellingShingle | Takatoshi Karasawa Martha Sibrian-Vazquez Robert M Strongin Peter S Steyger Identification of cisplatin-binding proteins using agarose conjugates of platinum compounds. PLoS ONE |
| title | Identification of cisplatin-binding proteins using agarose conjugates of platinum compounds. |
| title_full | Identification of cisplatin-binding proteins using agarose conjugates of platinum compounds. |
| title_fullStr | Identification of cisplatin-binding proteins using agarose conjugates of platinum compounds. |
| title_full_unstemmed | Identification of cisplatin-binding proteins using agarose conjugates of platinum compounds. |
| title_short | Identification of cisplatin-binding proteins using agarose conjugates of platinum compounds. |
| title_sort | identification of cisplatin binding proteins using agarose conjugates of platinum compounds |
| url | http://europepmc.org/articles/PMC3670892?pdf=render |
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