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The Calcium-Chelating Capability of Tetrahydrofuranic Moieties Modulates the Cytotoxicity of Annonaceous Acetogenins

Authors

  • Dr. Chih-Chuang Liaw,

    Corresponding author
    1. Department of Marine Biotechnology and Resources, National Sun Yat-sen University, 70 Lienhai Road, Kaohsiung 80424 (Taiwan)
    2. Graduate Institute of Pharmaceutical Chemistry, China Medical University, 91 Hsueh-Shih Road, Taichung 40402 (Taiwan)
    • Department of Marine Biotechnology and Resources, National Sun Yat-sen University, 70 Lienhai Road, Kaohsiung 80424 (Taiwan)
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  • Wen-Ying Liao,

    1. Graduate Institute of Pharmaceutical Chemistry, China Medical University, 91 Hsueh-Shih Road, Taichung 40402 (Taiwan)
    2. Genomics Research Centre, Academia Sinica, 128 Academia Road, Sec. 2, Taipei 115 (Taiwan)
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    • These authors contributed equally.

  • Dr. Chien-Sheng Chen,

    1. Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Sec. 2, Taipei 115 (Taiwan)
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  • Dr. Shu-Chuan Jao,

    1. Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Sec. 2, Taipei 115 (Taiwan)
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  • Prof. Yang-Chang Wu,

    1. Graduate Institute of Integrate Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung 40402 (Taiwan)
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    • These authors contributed equally.

  • Dr. Chia-Ning Shen,

    Corresponding author
    1. Genomics Research Centre, Academia Sinica, 128 Academia Road, Sec. 2, Taipei 115 (Taiwan)
    • Genomics Research Centre, Academia Sinica, 128 Academia Road, Sec. 2, Taipei 115 (Taiwan)
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  • Prof. Shih-Hsiung Wu

    Corresponding author
    1. Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Sec. 2, Taipei 115 (Taiwan)
    • Institute of Biological Chemistry, Academia Sinica, 128 Academia Road, Sec. 2, Taipei 115 (Taiwan)
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  • We thank Li-Wen Lo for assistance with confocal microscopy (Genomics Research Centre, Academia Sinica) and Dr. YuLin Lam (National University of Singapore) for English editing. This work was supported in part by National Science Council grant NSC97-2320-B-039-018-MY3 and Ministry of Education grant 97C031702 to C.-C.L. and by Academia Summit Project grant no. 5202402020-0 to C.-N.S. and no. 5202401023-2 to S.-H.W.

Abstract

original image

Gewaltsamer Zutritt: NMR-Spektroskopie und isotherme Titrationskalorimetrie zeigen, dass Calciumionen durch den hydroxylierten THF-Ring von Acetogeninen chelatisiert werden. Die gebildeten Komplexe vermitteln den Transport der Ca2+-Ionen durch Zellmembranen, was erhöhte intrazelluläre Calciumspiegel verursacht (siehe Bild). Diese Störung der intrazellulären Calciumhomöostase induziert die mitochondriale Depolarisation und vermittelt Zytotoxizität.

Ancillary