Transplatin is cytotoxic when photoactivated: enhanced formation of DNA cross-links

Pavla Heringova, Julie Woods, Fiona S. Mackay, Jana Kasparkova, Peter J. Sadler, Viktor Brabec

    Research output: Contribution to journalArticle

    62 Citations (Scopus)

    Abstract

    It is well-known that although cisplatin, [cis-[PtCl2(NH3)(2)], is an anticancer drug, its isomer transplatin is not cytotoxic. Here we show that transplatin is almost as cytotoxic as cisplatin when treated cells (human keratinocytes HaCaT and ovarian cancer A2780 cells) are irradiated with UVA light (50 min, 1.77 mW cm(-2)). Chemical studies show that light activates both chloride ligands of transplatin, and experiments on pSP73 plasmid DNA and a 23 base-pair DNA duplex show that irradiation can greatly enhance formation of interstrand cross-links and of DNA-protein cross-links (which are not formed in the dark). Comet assays showed that UVA irradiation of transplatin-treated cells resulted in an increased inhibition of H2O2-induced DNA migration, supporting the conclusion that the cytotoxicity of photoactivated transplatin is mainly due to formation of DNA interstrand and DNA-protein cross-links.

    Original languageEnglish
    Pages (from-to)7792-7798
    Number of pages7
    JournalJournal of Medicinal Chemistry
    Volume49
    Issue number26
    DOIs
    Publication statusPublished - 2006

    Cite this

    Heringova, P., Woods, J., Mackay, F. S., Kasparkova, J., Sadler, P. J., & Brabec, V. (2006). Transplatin is cytotoxic when photoactivated: enhanced formation of DNA cross-links. Journal of Medicinal Chemistry, 49(26), 7792-7798. https://doi.org/10.1021/jm0606692
    Heringova, Pavla ; Woods, Julie ; Mackay, Fiona S. ; Kasparkova, Jana ; Sadler, Peter J. ; Brabec, Viktor. / Transplatin is cytotoxic when photoactivated : enhanced formation of DNA cross-links. In: Journal of Medicinal Chemistry. 2006 ; Vol. 49, No. 26. pp. 7792-7798.
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    abstract = "It is well-known that although cisplatin, [cis-[PtCl2(NH3)(2)], is an anticancer drug, its isomer transplatin is not cytotoxic. Here we show that transplatin is almost as cytotoxic as cisplatin when treated cells (human keratinocytes HaCaT and ovarian cancer A2780 cells) are irradiated with UVA light (50 min, 1.77 mW cm(-2)). Chemical studies show that light activates both chloride ligands of transplatin, and experiments on pSP73 plasmid DNA and a 23 base-pair DNA duplex show that irradiation can greatly enhance formation of interstrand cross-links and of DNA-protein cross-links (which are not formed in the dark). Comet assays showed that UVA irradiation of transplatin-treated cells resulted in an increased inhibition of H2O2-induced DNA migration, supporting the conclusion that the cytotoxicity of photoactivated transplatin is mainly due to formation of DNA interstrand and DNA-protein cross-links.",
    author = "Pavla Heringova and Julie Woods and Mackay, {Fiona S.} and Jana Kasparkova and Sadler, {Peter J.} and Viktor Brabec",
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    Heringova, P, Woods, J, Mackay, FS, Kasparkova, J, Sadler, PJ & Brabec, V 2006, 'Transplatin is cytotoxic when photoactivated: enhanced formation of DNA cross-links', Journal of Medicinal Chemistry, vol. 49, no. 26, pp. 7792-7798. https://doi.org/10.1021/jm0606692

    Transplatin is cytotoxic when photoactivated : enhanced formation of DNA cross-links. / Heringova, Pavla; Woods, Julie; Mackay, Fiona S.; Kasparkova, Jana; Sadler, Peter J.; Brabec, Viktor.

    In: Journal of Medicinal Chemistry, Vol. 49, No. 26, 2006, p. 7792-7798.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Transplatin is cytotoxic when photoactivated

    T2 - enhanced formation of DNA cross-links

    AU - Heringova, Pavla

    AU - Woods, Julie

    AU - Mackay, Fiona S.

    AU - Kasparkova, Jana

    AU - Sadler, Peter J.

    AU - Brabec, Viktor

    PY - 2006

    Y1 - 2006

    N2 - It is well-known that although cisplatin, [cis-[PtCl2(NH3)(2)], is an anticancer drug, its isomer transplatin is not cytotoxic. Here we show that transplatin is almost as cytotoxic as cisplatin when treated cells (human keratinocytes HaCaT and ovarian cancer A2780 cells) are irradiated with UVA light (50 min, 1.77 mW cm(-2)). Chemical studies show that light activates both chloride ligands of transplatin, and experiments on pSP73 plasmid DNA and a 23 base-pair DNA duplex show that irradiation can greatly enhance formation of interstrand cross-links and of DNA-protein cross-links (which are not formed in the dark). Comet assays showed that UVA irradiation of transplatin-treated cells resulted in an increased inhibition of H2O2-induced DNA migration, supporting the conclusion that the cytotoxicity of photoactivated transplatin is mainly due to formation of DNA interstrand and DNA-protein cross-links.

    AB - It is well-known that although cisplatin, [cis-[PtCl2(NH3)(2)], is an anticancer drug, its isomer transplatin is not cytotoxic. Here we show that transplatin is almost as cytotoxic as cisplatin when treated cells (human keratinocytes HaCaT and ovarian cancer A2780 cells) are irradiated with UVA light (50 min, 1.77 mW cm(-2)). Chemical studies show that light activates both chloride ligands of transplatin, and experiments on pSP73 plasmid DNA and a 23 base-pair DNA duplex show that irradiation can greatly enhance formation of interstrand cross-links and of DNA-protein cross-links (which are not formed in the dark). Comet assays showed that UVA irradiation of transplatin-treated cells resulted in an increased inhibition of H2O2-induced DNA migration, supporting the conclusion that the cytotoxicity of photoactivated transplatin is mainly due to formation of DNA interstrand and DNA-protein cross-links.

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