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

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.

Nutraceuticals Synergistically Promote Osteogenesis in Cultured 7F2 Osteoblasts and Mitigate Inhibition of Differentiation and Maturation in Simulated Microgravity

“…In preliminary studies, and in line with prior results in other cell lines [ 16 , 38 , 39 , 40 ], we established that all nutraceuticals reduced short-term cell viability by ≤25% ( Table 1 ), a “shock effect” distinct from longer-term effects on cell proliferation. A similar effect has been described before in the literature for low levels of carnosic acid (6 µg/mL) in various cell lines [ 36 ].…”

“…Previous studies have explored the potential cytotoxicity of curcumin [ 19 ], carnosic acid [ 36 ], and zinc [ 37 ] for osteogenic cells, using several different viability assays. A fluorescent live/dead stain (calcein-AM ethidium homodimer-1, see Methods) was used to experimentally evaluate the effects of these nutraceuticals on the initial viability for 7F2 cells.…”

Health Effects of Coffee: Mechanism Unraveled?

“…These regions tend to bind to hydrophobic pockets of accessible proteins in tissues and may cause their denaturation and aggregation, which can lead to cell stress, including oxidative stress, and activation of the Nrf2 system as a protective response. High doses of phenolic compounds can be cytotoxic [72][73][74], but these conditions are usually not reached after a meal of plant foods. For instance, an upper safe limit for the ingestion of green tea catechins has been defined and set as 800 mg epigallocatechin-3-gallate [75].…”

Osteogenic differentiation of mesenchymal stem cells on random and aligned PAN/PPy nanofibrous scaffolds

“…These results are consistent with previous studies, which showed that D1 cells are as viable and active in 3D scaffolds as 2D surfaces. 51 MTT results, although an indirect measure of cell proliferation, concurred that PPy/PAN nanofiber scaffold was nontoxic, and cells were able to attach and grow on the scaffold, compared to the baseline values. The mineral deposition on PAN/PPy electrospun nanofibrous scaffolds was confirmed using Alizarin red staining after the 21 days of incubation period.…”