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KRN 5500 selectively disrupts the Golgi apparatus in HT-29 colon carcinoma cells

  1. Author:
    Kamishohara, M.
    Kenney, S.
    Vistica, D.
    Sausville, E.
    1. Year of Conference: 1997
  2. Conference Name: Annual Meeting of the American Association for Cancer Research
    1. 38
    2. Pages: A1528
  4. Type of Work: Meeting Abstract
  1. Abstract:

    KRN 5500 is a semisynthetic spicamycin analog consisting of a C14 unsaturated fatty acid, glycine, aminoheptose and adenine. The compound has both in vitro and in vivo activity against a variety of human tumor cell lines including those derived from colon and breast. Recent studies in this laboratory have utilized the HT-29 colon carcinoma cell line in an attempt to identify specific cellular lesions which may contribute to the cytotoxicity of KRN 5500. Uptake of radiolabeled KRN 5500 by the HT-29 colon carcinoma and a variant with acquired resistance was found to be identical, suggesting that intracellular disposition of the drug may differ in sensitive and resistant cell lines. A series of experiments revealed that KRN 5500 produces a rapid conversion of the normal stack-like morphology of the Golgi apparatus to one which exhibits swollen cisternae. The additional observation that KRN 5500 produces a concentration dependent effect on mannose incorporation suggests that this drug may affect protein flow/glycosylation/secretion in sensitive cell lines.

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