Radiosensitization of cancer cells by hydroxychalcones

Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Bioorganic & medicinal chemistry letters (Impact Factor: 2.42). 10/2010; 20(20):5997-6000. DOI: 10.1016/j.bmcl.2010.08.081
Source: PubMed


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.

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