title: 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.affiliation: Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Rory
authors.initials: R
authors.lastname: Pruitt
authors.forename: Nidhish
authors.initials: N
authors.lastname: Sasi
authors.forename: Michael L
authors.initials: ML
authors.lastname: Freeman
authors.forename: Konjeti R
authors.initials: KR
authors.lastname: Sekhar
mesh_terms: D000230:Adenocarcinoma / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000532:radiotherapy*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
chemical_list: C107497:2',5'-dihydroxychalcone; C552398:2,2'-dihydroxychalcone; D047188:Chalcones; D011838:Radiation-Sensitizing Agents
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