Outlines:

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)

References:

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).