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Cytotoxic Tolerance of Healthy and Cancerous Bone Cells to Anti-microbial Phenolic Compounds Depend on Culture Conditions

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Abstract

Carnosol and carnosic acid are polyphenolic compounds found in rosemary and sage with known anti-oxidant, anti-inflammatory, and anti-microbial properties. Here, we addressed the potential use of carnosol and carnosic acid for in vitro bone tissue engineering applications, specifically depending on their cytotoxic effects on bone marrow stromal and stem cells, and osteosarcoma cells in monolayer and 3D cultures. Carnosol and carnosic acid displayed a bacteriostatic effect on Gram-positive bacteria, especially on S. aureus. The viability results indicated that bone marrow stromal cells and bone marrow stem cells were more tolerant to the presence of carnosol compared to osteosarcoma cells. 3D culture conditions increased this tolerance further for healthy cells, while not affecting the cytotoxic potential of carnosol for osteosarcoma cells. Carnosic acid was found to be more cytotoxic for all cell types used in the study. Results suggest that phenolic compounds might have potential use as anti-microbial and anti-carcinogenic agents for bone tissue engineering with further optimization for controlled release.

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Acknowledgements

We are thankful for the helpful discussions with Ozden Yalcın-Ozuysal, PhD, and Ferda Soyer Donmez, PhD. The Izmir Institute of Technology, Biotechnology and Bioengineering Research Center is also appreciated for instrumental support.

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Financial support was from The Scientific and Technological Research Council of Turkey (215S862 - EO) and Turkish Academy of Sciences (Young Investigator Award - EO).

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Correspondence to Engin Ozcivici.

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Karadas, O., Mese, G. & Ozcivici, E. Cytotoxic Tolerance of Healthy and Cancerous Bone Cells to Anti-microbial Phenolic Compounds Depend on Culture Conditions. Appl Biochem Biotechnol 188, 514–526 (2019). https://doi.org/10.1007/s12010-018-02934-7

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