[PROC. AMER. ASSOC. CANCER RES. 40, March 1999]
Copyright © 1999 by the American Association for Cancer Research
#1993 Cytotoxic effects of MGI 114 are independent of tumor suppressor gene p53 and p21 expression. 1Izbicka, E., 1Davidson, K., 1Lawrence, R., 2Cote, R., 1Rha, S.Y., 3MacDonald, J.R., 1Von Hoff, D.D. 1Institute for Drug Development, CTRC, San Antonio, TX 78245, 2UTSC, Los Angeles, CA 90033, and 1MGI Pharma, Inc., Minnetonka, MN 55343.
MGI 114, an analog of illudin S, shows potent activity against a broad range 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 lines (MCF7, MDA.MB.468, EJ1, J82, SCaBER, KG-1, HL60, and IMR-90) with different status 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 MCF7 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 µg/ml in 1 h exposure and with 0.01, 0.1 and 1.0 µg/ml MGI114 in a continuous exposure. Cell numbers were measured at days 2, 4, and 7. MGI 114 suppressed early growth in all cell lines after 1 h exposure at the two highest levels and at all concentrations in a continuous exposure. Some cells partly recovered 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. In summary, MGI 114 effectively inhibits growth of human cancer cells regardless of their p53 and WAF1 status. Supported in part by a grant from MGI Pharma, Inc.
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I think this abstract might have been posted elsewhere by Rick (they all look very similar to me). "In summary, MGI 114 effectively inhibits growth of human cancer cells regardless of their p53 and WAF1 status." Sounds to me like MOGN is the Lone Ranger and MGI 114 is a Silver Bullet. Perhaps someone competent in this area can comment... |
