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Carnosol, radiation and melanoma: a translational possibility

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Abstract

Purpose

To compare the genoprotective and radioprotective effect of carnosol (COL) against damage induced by ionizing radiation with similar effects produced by different antioxidant compounds.

Methods

The genoprotective effect was studied by means of the micronucleus test for antimutagenic activity in which the reduction in the frequency of micronuclei was evaluated in cytokinesis-blocked cells of human lymphocytes. The radioprotective effects were studied by cell viability test (MTT) in PNT2 (normal prostate) and B16F10 (melanoma) cell lines when they were administered before exposure to different X-ray doses (4, 6, 8, 10 and 0 Gy).

Results

Carnosol shows a significant genoprotective capacity (p < 0.001) against radiation with a protection factor of 50 %, and a dose-reduction factor of 4.3. Cell survival obtained with COL administered before exposure to 10 Gy of X-rays showed a protection factor of 55.1 %, eliminating 39 % of radiation-induced cell death in normal epithelial cells of prostate (PNT2) (p < 0.001). However, in the melanoma cell lines (B16F10) assayed, COL acted not as a radioprotector, but as a sensitizing agent increasing the cellular death by 34 % (p < 0.01) and producing an enhancement ratio of 2.12.

Conclusions

Carnosol may be developed as a radioprotective agent in the non-tumoral cells. However, in the B10F16 melanoma cells, melanogenesis is activated by COL leading to redistribution of the enzymatic balances of glutathione and cysteine-lyase production, which could compromise the intracellular redox defence system. This effect appears as an increase in the capacity of ionizing radiation-induced damage, and thus exhibits a paradoxical protective effect of COL on melanoma cells.

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Acknowledgments

This report was supported by a grant from the National Spanish R&D Programme CENIT (Acronym:SENIFOOD); D.G. Achel was able to take part in this study because of a sponsored fellowship from IAEA and A. Olivares thanks to a fellowship from the Seneca Foundation.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Radiology and Physical Medicine Department, Faculty of Medicine/Dentistry, University of Murcia, 30100 Espinardo, Murcia, Spain

    M. Alcaraz, A. Olivares, E. Olmos, M. Alcaraz-Saura & J. Castillo

  2. Applied Radiation Biology Centre, Radiological and Medical Sciences Research Institute, Ghana Atomic Energy Commission, Legon-Accra, Ghana

    D. G. Achel

Authors
  1. M. Alcaraz
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  2. D. G. Achel
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  3. A. Olivares
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  4. E. Olmos
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  5. M. Alcaraz-Saura
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  6. J. Castillo
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Corresponding author

Correspondence to M. Alcaraz.

Additional information

This report was supported by a grant from the National Spanish R&D Programme CENIT of the Spanish Ministry of Science and Technology denominated “Industrial research diets and food with specific features for the elderly” (Acronym: SENIFOOD); DG. Achel was able to take part in this study because of a sponsored fellowship (GHA/0021) from International Atomic Energy Agency (IAEA) and A. Olivares thanks to a grant from the Seneca Foundation (Coordination Research Centre of the Region of Murcia, Spain).

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Alcaraz, M., Achel, D.G., Olivares, A. et al. Carnosol, radiation and melanoma: a translational possibility. Clin Transl Oncol 15, 712–719 (2013). https://doi.org/10.1007/s12094-012-0994-9

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  • DOI: https://doi.org/10.1007/s12094-012-0994-9

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