期刊
MOLECULAR ONCOLOGY
卷 2, 期 1, 页码 70-80出版社
WILEY
DOI: 10.1016/j.molonc.2008.02.004
关键词
Mutant p53 reactivation; STIMA-1; CP-31398; Apoptosis; Cancer therapy
类别
资金
- Swedish Cancer Society (Cancerfonden)
- Cancer Society of Stockholm (Cancerforeningen)
- Ingabritt & Arne Lundberg Foundation
- Karolinska Institute
- EU 6th Framework Program
Reactivation of mutant p53 in human tumor cells should induce cell death by apoptosis and thus eliminate the tumor. Several small molecules that reactivate mutant p53 have been identified. Here we show that STIMA-1, a low molecular weight compound with some structural similarities to the previously identified molecule CP-31398, can stimulate mutant p53 DNA binding in vitro and induce expression of p53 target proteins and trigger apoptosis in mutant p53-expressing human tumor cells. Human diploid fibroblasts are significantly more resistant to STIMA-1 than mutant or wild type p53-carrying tumor cells. STIMA-1 may provide new insights into possible mechanisms of mutant p53 reactivation and thus facilitate the development of novel anticancer drugs that target mutant p53-carrying tumors. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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