Screening of inhibitors of mitogenic activity of EGF.


Specific inhibitors of growth factors should be useful to elucidate the mechanism of action and relationship between growth factors and oncogenesis. In addition, they are expected to have a new type of antitumor activity. EGF (epidermal growth factor) is a homologous protein to transforming growth factor alpha and both growth factors share the same receptor. Therefore, the inhibitor of EGF is expected as a growth inhibitor of tumor cells.
Balb/MK cells were cultured in minimal essential medium (MEM) containing a calcium concentration of 0.05mM supplemented with 5 ng/ml of EGF and 10% of FCS. At confluent growth stage, culture medium was changed to fresh low calcium MEM medium without EGF and FCS. Mitogenic activity of EGF can be measured by the incorporation of [3H]thymidine into quiescent Balb/MK cells 17 hours after addition of EGF. The incorporation of [3H] thymidine into Balb/MK cells was measured in the presence or absence of test compounds.

Inhibition of [3H]thymidine uptake into EGF-stimulated Balb/MK cells by reveromycins. ○Reveromycin A, ●reveromycin B, ■reveromycin C, .▲(Ref:1)


  1. H. Takahashi, H. Osada, H. Koshino, M. Sasaki, R. Onose, M. Nakakoshi, M. Yoshihama, K. Isono
    Reveromycins, new inhibitors of eukaryotic cell growth. II. Biological activities.
    J. Antibiotics, 45, 1414-1419 (1992).

  2. H. Osada, T. Sonoda, H. Kusakabe, K. Isono.
    Epiderstatin, a new inhibitor of the mitogenic activity induced by epidermal growth factor. I. Taxonomy, fermentation, isolation and characterization.
    J. Antibiotics, 42, 1599-1606 (1989).

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