期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 293, 期 12, 页码 4262-4276出版社
ELSEVIER
DOI: 10.1074/jbc.RA117.000950
关键词
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资金
- Hungarian National, Research, Development and Innovation Office [OTKA 104956]
- Swiss Cancer Leagu [LB692]
- Seeds of Science
- Winthrop P. Rockefeller Cancer Institute
- Creighton University
- MRC [MC_EX_G0901534] Funding Source: UKRI
- NATIONAL CANCER INSTITUTE [P30CA016058, F30CA216966] Funding Source: NIH RePORTER
- Medical Research Council [MC_EX_G0901534] Funding Source: researchfish
p53 is an important tumor-suppressor protein that is mutated in more than 50% of cancers. Strategies for restoring normal p53 function are complicated by the oncogenic properties of mutant p53 and have not met with clinical success. To counteract mutant p53 activity, a variety of drugs with the potential to reconvert mutant p53 to an active wildtype form have been developed. However, these drugs are associated with various negative effects such as cellular toxicity, nonspecific binding to other proteins, and inability to induce a wildtype p53 response in cancer tissue. Here, we report on the effects of a curcumin analog, HO-3867, on p53 activity in cancer cells from different origins. We found that HO-3867 covalently binds to mutant p53, initiates a wildtype p53-like anticancer genetic response, is exclusively cytotoxic toward cancer cells, and exhibits high anticancer efficacy in tumor models. In conclusion, HO-3867 is a p53 mutant-reactivating drug with high clinical anticancer potential.
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