Radiosensitizing Effect of Rosmarinic Acid in Metastatic Melanoma B16F10 Cells
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Alcaraz, Miguel
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Alcaraz-Saura, Miguel
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Univ Murcia, Radiol & Phys Med Dept, Fac Med Dent, Espinardo 30100, Murcia, SpainUniv Murcia, Radiol & Phys Med Dept, Fac Med Dent, Espinardo 30100, Murcia, Spain
Alcaraz-Saura, Miguel
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Achel, Daniel Gyingiri
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Ghana Atom Energy Commiss, Appl Radiat Biol Ctr, Radiol & Med Sci Res Inst, Legon, GhanaUniv Murcia, Radiol & Phys Med Dept, Fac Med Dent, Espinardo 30100, Murcia, Spain
Achel, Daniel Gyingiri
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Olivares, Amparo
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Univ Murcia, Radiol & Phys Med Dept, Fac Med Dent, Espinardo 30100, Murcia, SpainUniv Murcia, Radiol & Phys Med Dept, Fac Med Dent, Espinardo 30100, Murcia, Spain
Olivares, Amparo
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Antonio Lopez-Morata, Jose
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Univ Murcia, Radiol & Phys Med Dept, Fac Med Dent, Espinardo 30100, Murcia, SpainUniv Murcia, Radiol & Phys Med Dept, Fac Med Dent, Espinardo 30100, Murcia, Spain
Antonio Lopez-Morata, Jose
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Castillo, Julian
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Univ Murcia, Radiol & Phys Med Dept, Fac Med Dent, Espinardo 30100, Murcia, SpainUniv Murcia, Radiol & Phys Med Dept, Fac Med Dent, Espinardo 30100, Murcia, Spain
Castillo, Julian
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[1] Univ Murcia, Radiol & Phys Med Dept, Fac Med Dent, Espinardo 30100, Murcia, Spain
[2] Ghana Atom Energy Commiss, Appl Radiat Biol Ctr, Radiol & Med Sci Res Inst, Legon, Ghana
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.