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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Curcumin-altered p53-response genes regulate radiosensitivity in p53-mutant Ewing's sarcoma cells
J Veeraraghavan1, M Natarajan, T S Herman
1Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Curcumin enhances radiation therapy in p53 mutant Ewing sarcoma cells by affecting apoptosis and DNA damage. This suggests curcumin as a potential radiosensitizer, though its p53-independent effects require further study.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- Curcumin exhibits antitumor properties, including radiosensitization, by targeting molecules like p53.
- Ewing's sarcoma (ES) is a cancer often characterized by p53 mutations.
Purpose of the Study:
- To investigate the radiosensitizing effect of curcumin in p53-mutant Ewing's sarcoma (ES) cells.
- To explore curcumin's impact on p53 downstream targets and related cellular processes.
Main Methods:
- ES cells were treated with radiation and/or curcumin.
- Transcriptional and translational levels of p53 downstream targets were analyzed.
- Apoptosis, DNA fragmentation, cell survival, and clonal expansion were assessed.
Main Results:
- Curcumin modulated the expression of p21, Bax, BclXl, and Mcl1 in response to radiation.
- Radiation with or without curcumin did not alter p53 levels.
- Curcumin enhanced radiation-induced apoptosis, DNA fragmentation, cytotoxicity, and clonal expansion.
Conclusions:
- Curcumin demonstrates radiosensitizing potential in p53-mutant ES cells.
- The radiosensitization appears to be mediated through the regulation of IR-modulated p53-response genes.
- Further research is needed to understand the p53-independent mechanisms of curcumin's action.
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