PRIMA-1MET synergizes with cisplatin to induce tumor cell apoptosis
Open Access
- 28 February 2005
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 24 (21), 3484-3491
- https://doi.org/10.1038/sj.onc.1208419
Abstract
Mutant p53-carrying tumors are often more resistant to chemotherapeutical drugs. We demonstrate here that the mutant p53-reactivating compound PRIMA-1MET acts synergistically with several chemotherapeutic drugs to inhibit tumor cell growth. Combined treatment with cisplatin and PRIMA-1MET resulted in a synergistic induction of tumor cell apoptosis and inhibition of human tumor xenograft growth in vivo in SCID mice. The induction of mutant p53 levels by chemotherapeutic drugs is likely to increase the sensitivity of tumor cells to PRIMA-1MET. Thus, the combination of PRIMA-1MET with currently used chemotherapeutic drugs may represent a novel and more efficient therapeutic strategy for treatment of mutant p53-carrying tumors.Keywords
This publication has 18 references indexed in Scilit:
- Senescence, apoptosis and therapy — cutting the lifelines of cancerNature Reviews Cancer, 2003
- Chemosensitivity linked to p73 functionCancer Cell, 2003
- Stabilization of p53 by CP-31398 Inhibits Ubiquitination without Altering Phosphorylation at Serine 15 or 20 or MDM2 BindingMolecular and Cellular Biology, 2003
- TP53and breast cancerHuman Mutation, 2003
- The p53–Mdm2 module and the ubiquitin systemSeminars in Cancer Biology, 2002
- Live or let die: the cell's response to p53Nature Reviews Cancer, 2002
- Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compoundNature Medicine, 2002
- Pharmacological Rescue of Mutant p53 Conformation and FunctionScience, 1999
- Disruption of p53 in human cancer cells alters the responses to therapeutic agentsJCI Insight, 1999
- An Information-Intensive Approach to the Molecular Pharmacology of CancerScience, 1997