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Curcumin impairs tumor suppressor p53 function in colon cancer cells
Philip J Moos1, Kornelia Edes, James E Mullally
1Department of Oncological Sciences and Department of Medicinal Chemistry, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT 84112, USA. philip.moos@hci.utah.edu
Carcinogenesis
|April 20, 2004
Summary
Curcumin, a potential cancer-preventive compound, disrupts the tumor suppressor p53 protein. This action inhibits p53
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- Curcumin (diferuloylmethane) shows promise as a human chemopreventive agent.
- It inhibits NF-kappaB transcription and enzymes like lipoxygenase and cyclooxygenase, which promote tumor growth.
- Curcumin's reactive moiety is known to repress NF-kappaB.
Purpose of the Study:
- To investigate curcumin's effect on the tumor suppressor protein p53.
- To determine if curcumin's electrophilic moiety impacts p53 function, similar to other compounds.
Main Methods:
- Investigated curcumin's interaction with p53 protein structure and function.
- Assessed effects on p53 serine phosphorylation, DNA binding, and transactivation.
- Evaluated curcumin's impact on p53-mediated cell cycle arrest.
Main Results:
- Curcumin disrupts the p53 protein conformation.
- This disruption impairs p53's ability to be phosphorylated, bind DNA, and activate target genes.
- Curcumin inhibits p53-mediated cell cycle arrest.
Conclusions:
- Curcumin negatively affects the tumor suppressor p53 protein.
- This mechanism may contribute to curcumin's chemopreventive properties.
- Further research is warranted to explore curcumin's therapeutic potential in cancer.