TY - JOUR T1 - Radiosensitizing Effect of Rosmarinic Acid in Metastatic Melanoma B16F10 Cells JF - Anticancer Research JO - Anticancer Res SP - 1913 LP - 1921 VL - 34 IS - 4 AU - MIGUEL ALCARAZ AU - MIGUEL ALCARAZ-SAURA AU - DANIEL GYINGIRI ACHEL AU - AMPARO OLIVARES AU - JOSÉ ANTONIO LÓPEZ-MORATA AU - JULIÁN CASTILLO Y1 - 2014/04/01 UR - http://ar.iiarjournals.org/content/34/4/1913.abstract N2 - Background: Rosmarinic acid is an ester of caffeic acid with interesting biological activities including antioxidant effects and scavenging of oxygen-free radicals. Aim: 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. Materials and 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. Conclusion: 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. ER -