Radiosensitization of cancer cells by hydroxychalcones.

Abstract

Radiation sensitization is significantly increased by proteotoxic stress, such as a heat shock. We undertook an investigation, seeking to identify natural products that induced proteotoxic stress and then determined if a compound exhibited radiosensitizing properties. The hydroxychalcones, 2',5'-dihydroxychalcone (D-601) and 2,2'-dihydroxychalcone (D-501), were found to activate heat shock factor 1 (Hsf1) and exhibited radiation sensitization properties in colon and pancreatic cancer cells. The radiosensitization ability of D-601 was blocked by pretreatment with α-napthoflavone (ANF), a specific inhibitor of cytochrome P450 1A2 (CYP1A2), suggesting that the metabolite of D-601 is essential for radiosensitization. The study demonstrated the ability of hydroxychalcones to radiosensitize cancer cells and provides new leads for developing novel radiation sensitizers.

• Authors: Rory Pruitt, Nidhish Sasi, Michael L Freeman, Konjeti R Sekhar
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 20 Pg. 5997-6000 (Oct 15 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 20826087 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• 2',5'-dihydroxychalcone
• 2,2'-dihydroxychalcone
• Chalcones
• Radiation-Sensitizing Agents

Topics

• Adenocarcinoma (radiotherapy)
• Cell Line, Tumor
• Chalcones (pharmacology)
• Colonic Neoplasms (radiotherapy)
• Humans
• Pancreatic Neoplasms (radiotherapy)
• Radiation-Sensitizing Agents (pharmacology)