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
Hauptverfasser: Imai, Ryosuke, Komeda, Seiji, Shimura, Mari, Tamura, Sachiko, Matsuyama, Satoshi, Nishimura, Kohei, Rogge, Ryan, Matsunaga, Akihiro, Hiratani, Ichiro, Takata, Hideaki, Uemura, Masako, Iida, Yutaka, Yoshikawa, Yuko, Hansen, Jeffrey C., Yamauchi, Kazuto, Kanemaki, Masato T., Maeshima, Kazuhiro
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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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep24712