title: Resveratrol sensitization of DU145 prostate cancer cells to ionizing radiation is associated to ceramide increase.
abstract: Radiotherapy is an established therapeutic modality for prostate cancer. Since it is well known that radiotherapy is limited due to its severe toxicity towards normal cells at high dose and minimal effect at low dose, the search for biological compounds that increase the sensitivity of tumors cells to radiation may improve the efficacy of therapy. Resveratrol, a natural antioxidant, was shown to inhibit carcinogenesis in animal models, and to block the process of tumor initiation and progression. The purpose of this study was to examine whether or not resveratrol can sensitize DU145, an androgen-independent human prostate cancer cell line, to ionizing radiation. We report here that DU145 cells are resistant to ionizing radiation-induced cell death, but pretreatment with resveratrol significantly enhances cell death. Resveratrol acts synergistically with ionizing radiation to inhibit cell survival in vitro. Resveratrol also potentiates ionizing radiation-induced ceramide accumulation, by promoting its de novo biosynthesis. This confirms ceramide as an effective mediator of the anticancer potential induced by resveratrol.
authors.affiliation: Laboratory of Biochemistry & Mol Biology, San Paolo Medical School, University of Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Scarlatti
authors.forename: Giusy
authors.initials: G
authors.lastname: Sala
authors.forename: Clara
authors.initials: C
authors.lastname: Ricci
authors.forename: Claudio
authors.initials: C
authors.lastname: Maioli
authors.forename: Franco
authors.initials: F
authors.lastname: Milani
authors.forename: Marco
authors.initials: M
authors.lastname: Minella
authors.forename: Marco
authors.initials: M
authors.lastname: Botturi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ghidoni
mesh_terms: D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D002518:Ceramides; D011838:Radiation-Sensitizing Agents; D013267:Stilbenes; D000077185:Resveratrol