MGI 114, an analog of illudin S, shows potent activity against a broad rang
e of human tumors in vitro and in vivo, including drug resistant tumors. In
this study we examined cytotoxicity of MGI 114 against human tumor cell li
nes (MCF7, MDA.MB.468, EJ1, J82, SCaBER, KG-1, HL60, and IMR-90) with diffe
ring expression of p53 and/or p21 (WAF1) tumor suppressor genes. Only MCF7
and IMR-90 express the wild type p53, WAF1 is present in high levels in MCF
7 and SCaBER. WAF1 expression can be induced in KG-1, HL60, and IMR-90. The
cells were treated with MGI 114 at 0.1, 1.0 and 10 mu g/ml in 1 h exposure
and with 0.01, 0.1 and 1.0 mu g/ml MGI 114 in a continuous exposure. Cell
numbers were measured at days 2, 4 and 7. MGI 114 suppressed growth in all
cell lines at day 2 after I h exposure at the two highest concentrations an
d at all concentrations in a continuous exposure. Some cells partly recover
ed from the inhibition by day 4. Expression of WAF1 had no apparent effect
on growth suppression by MGI 114 however, cells with inducible WAF1 showed
slower recovery from MGI 114 inhibition in comparison with the cells under
non-permissive conditions. Overall, MGI 114 effectively inhibited growth of
human cancer cells regardless of their p53 and WAF1 status.