Biomaterial Database

Curcumin-altered p53-response genes regulate radiosensitivity in p53-mutant Ewing's sarcoma cells. 2010

J Veeraraghavan, and M Natarajan, and T S Herman, and N Aravindan

Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.

OBJECTIVE Curcumin has been demonstrated to have antitumor effects including radiosensitization by modulating many molecular targets including p53. Herein, we investigated the radiosensitizing effect of curcumin in p53 mutant Ewing's sarcoma (ES) cells. METHODS Cells exposed to radiation with or without curcumin were examined for transcriptional and translational levels of p53 downstream targets and its influence in regulated apoptosis, DNA fragmentation, cell survival and clonal expansion. RESULTS Curcumin significantly caused radiation induced expression of p21 and Bax, and reduced BclXl, Mcl1 with only marginal Bcl2 modulation. As a positive control to the study, both transcriptional and translational levels of p53 remained unchanged after radiation with/without curcumin. Conversely, curcumin caused radiation-induced apoptosis and DNA fragmentation. Consistently, curcumin enhanced radiation-induced cytotoxicity and clonal expansion. CONCLUSIONS These results suggest that curcumin potentially radiosensitizes p53-mutant ES cells by regulating IR-modulated p53-response genes. However, the curcumin-associated p53-independent regulation of downstream targets remains to be explored.

UI	MeSH Term	Description	Entries
D007259	Infrared Rays	That portion of the electromagnetic spectrum usually sensed as heat. Infrared wavelengths are longer than those of visible light, extending into the microwave frequencies. They are used therapeutically as heat, and also to warm food in restaurants.	Heat Waves,Heat Wave,Infrared Ray,Ray, Infrared,Rays, Infrared,Wave, Heat,Waves, Heat
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D011836	Radiation Tolerance	The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.	Radiation Sensitivity,Radiosensitivity,Sensitivity, Radiation,Tolerance, Radiation,Radiation Sensitivities,Radiation Tolerances,Radiosensitivities,Sensitivities, Radiation,Tolerances, Radiation
D011838	Radiation-Sensitizing Agents	Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.	Radiation Sensitizer,Radiosensitizing Agent,Radiosensitizing Agents,Agents, Radiation-Sensitizing,Radiation Sensitizers,Radiation Sensitizing Agents,Radiation-Sensitizing Drugs,Radiation-Sensitizing Effect,Radiation-Sensitizing Effects,Radiosensitizing Drugs,Radiosensitizing Effect,Radiosensitizing Effects,Agent, Radiosensitizing,Agents, Radiation Sensitizing,Agents, Radiosensitizing,Drugs, Radiation-Sensitizing,Drugs, Radiosensitizing,Effect, Radiation-Sensitizing,Effect, Radiosensitizing,Effects, Radiation-Sensitizing,Effects, Radiosensitizing,Radiation Sensitizing Drugs,Radiation Sensitizing Effect,Radiation Sensitizing Effects,Sensitizer, Radiation,Sensitizers, Radiation,Sensitizing Agents, Radiation
D003131	Combined Modality Therapy	The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.	Multimodal Treatment,Therapy, Combined Modality,Combined Modality Therapies,Modality Therapies, Combined,Modality Therapy, Combined,Multimodal Treatments,Therapies, Combined Modality,Treatment, Multimodal,Treatments, Multimodal
D003474	Curcumin	A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes.	1,6-Heptadiene-3,5-dione, 1,7-bis(4-hydroxy-3-methoxyphenyl)-, (E,E)-,Curcumin Phytosome,Diferuloylmethane,Mervia,Turmeric Yellow,Phytosome, Curcumin,Yellow, Turmeric
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012512	Sarcoma, Ewing	A malignant tumor of the bone which always arises in the medullary tissue, occurring more often in cylindrical bones. The tumor occurs usually before the age of 20, about twice as frequently in males as in females.	Ewing's Tumor,Sarcoma, Ewing's,Ewing Sarcoma,Ewing Tumor,Ewing's Sarcoma,Ewings Sarcoma,Ewings Tumor,Sarcoma, Ewings,Tumor, Ewing,Tumor, Ewing's
D014158	Transcription, Genetic	The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.	Genetic Transcription
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal