title: Radiosensitizing effect of rosmarinic acid in metastatic melanoma B16F10 cells.
abstract: BACKGROUND
  Rosmarinic acid is an ester of caffeic acid with interesting biological activities including antioxidant effects and scavenging of oxygen-free radicals.
  
  
  OBJECTIVE
  To determine the potentially paradoxical effect of rosmarinic acid, typically being radioprotective when applied to non-tumorous cells, yet conversely displaying a sensitizing action when applied to metastatic B16F10 melanoma cells.
  
  
  METHODS
  The genoprotective effect was studied by means of micronucleus tests for anti-mutagenic activity in which the reduction in the frequency of micronuclei was evaluated using cytokinesis-blocked human lymphocytes. The radioprotective effect was studied via a cell viability test in PNT2 (human prostate epithelium) and B16F10 melanoma cells.
  
  
  RESULTS
  Rosmarinic acid exhibits a significant genoprotective capacity (p<0.001) against X-rays with a protection factor of 58%, and a dose reduction factor of 7.2. Cell survival obtained after exposure to 10 Gy of X-rays showed a protection factor of 47.5%, thus eliminating 29.1% of radiation-induced cell death in normal prostate epithelial cells (p<0.001). However, in metastatic B16F10 melanoma cells, rosmarinic acid acted not as a radioprotector, but as a sensitizing agent, increasing cellular death by 42% (p<0.001), with an enhancement ratio of 2.36.
  
  
  CONCLUSIONS
  Rosmarinic acid has an increased capacity for producing radio-induced damage, and thus a paradoxical damaging effect in melanoma cells. Potentially, research into substances such as rosmarinic acid could help clarify mechanisms that provide protection on healthy normal cells, while exclusively damaging neoplastic cells, thus presenting a new strategy for patients undergoing radiotherapy for cancer.
authors.affiliation: Radiology and Physical Medicine Department, Faculty of Medicine/Dentistry, University of Murcia, 30100-Espinardo (Murcia), Spain. mab@um.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Alcaraz
authors.forename: Miguel
authors.initials: M
authors.lastname: Alcaraz-Saura
authors.forename: Daniel Gyingiri
authors.initials: DG
authors.lastname: Achel
authors.forename: Amparo
authors.initials: A
authors.lastname: Olivares
authors.forename: José Antonio
authors.initials: JA
authors.lastname: López-Morata
authors.forename: Julián
authors.initials: J
authors.lastname: Castillo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology*; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000528:radiation effects; D009362:Neoplasm Metastasis; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D000097123:Rosmarinic Acid
chemical_list: D002934:Cinnamates; D053630:Depsides; D011838:Radiation-Sensitizing Agents; D000097123:Rosmarinic Acid
keywords: B16F10 cells; PNT2; Radiation effects; melanoma; micronuclei; radioprotectors; radiosensitizers; rosmarinic acid