Chromatin folding and DNA replication inhibition mediated by a highly antitumor-active tetrazolato-bridged dinuclear platinum(II) complex
Chromatin DNA must be read out for various cellular functions and copied for the next cell division. These processes are targets of many anticancer agents. Platinum-based drugs, such as cisplatin, have been used extensively in cancer chemotherapy. The drug–DNA interaction causes DNA crosslinks and s...
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Veröffentlicht in: | Scientific reports 2016-04, Vol.6 (1), p.24712-24712, Article 24712 |
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Sprache: | eng |
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Zusammenfassung: | Chromatin DNA must be read out for various cellular functions and copied for the next cell division. These processes are targets of many anticancer agents. Platinum-based drugs, such as cisplatin, have been used extensively in cancer chemotherapy. The drug–DNA interaction causes DNA crosslinks and subsequent cytotoxicity. Recently, it was reported that an azolato-bridged dinuclear platinum(II) complex, 5-H-Y, exhibits a different anticancer spectrum from cisplatin. Here, using an interdisciplinary approach, we reveal that the cytotoxic mechanism of 5-H-Y is distinct from that of cisplatin. 5-H-Y inhibits DNA replication and also RNA transcription, arresting cells in the S/G2 phase and are effective against cisplatin-resistant cancer cells. Moreover, it causes much less DNA crosslinking than cisplatin and induces chromatin folding. 5-H-Y will expand the clinical applications for the treatment of chemotherapy-insensitive cancers. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/srep24712 |