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Carcinogenic Aspects of Protein Phosphatase 1 and 2A Inhibitors

  • Chapter
Marine Toxins as Research Tools

Part of the book series: Progress in Molecular and Subcellular Biology ((MMB,volume 46))

Abstract

Okadaic acid is functionally a potent tumor promoter working through inhibition of protein phosphatases 1 and 2A (PP1 and PP2A), resulting in sustained phosphorylation of proteins in cells. The mechanism of tumor promotion with oka-daic acid is thus completely different from that of the classic tumor promoter phorbol ester. Other potent inhibitors of PP1 and PP2A – such as dinophysistoxin-1, calyculins A–H, microcystin-LR and its derivatives, and nodularin – were isolated from marine organisms, and their structural features including the crystal structure of the PP1-inhibitor complex, tumor promoting activities, and biochemical and biological effects, are here reviewed. The compounds induced tumor promoting activity in three different organs, including mouse skin, rat glandular stomach and rat liver, initiated with three different carcinogens. The results indicate that inhibition of PP1 and PP2A is a general mechanism of tumor promotion applicable to various organs. This study supports the concept of endogenous tumor promoters in human cancer development.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, 770-8514, Japan

    Hirota Fujiki

  2. Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, 362-0806, Japan

    Masami Suganuma

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  1. Hirota Fujiki
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  2. Masami Suganuma
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Editors and Affiliations

  1. Hokkaido University, 3-1-1 Minato-cho, Hakodate, 041-8611, Japan

    Nobuhiro Fusetani (Faculty of Fisheries Sciences) (Faculty of Fisheries Sciences)

  2. Department of Pharmacology & Therapeutics, University of Florida, P.O. Box 100267, Gainesville, FL, 32610-0267, USA

    William Kem

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Fujiki, H., Suganuma, M. (2009). Carcinogenic Aspects of Protein Phosphatase 1 and 2A Inhibitors. In: Fusetani, N., Kem, W. (eds) Marine Toxins as Research Tools. Progress in Molecular and Subcellular Biology, vol 46. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-87895-7_8

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