carnosol and Osteosarcoma

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.

Topics: Abietanes; Animals; Anti-Infective Agents; Anticarcinogenic Agents; Bone Neoplasms; Cell Culture Techniques; Cell Line; Cell Line, Tumor; Cell Survival; Drug Resistance, Neoplasm; Humans; Limb Salvage; Mesenchymal Stem Cells; Mice; Osteosarcoma; Tissue Engineering

Carnosol is an anti-oxidant and anti-inflammatory compound from rosemary. In this paper, we investigated antitumor activity of carnosol against human osteosarcoma cells. We found the viability of human osteosarcoma MG-63 cells was significantly decreased in the presence of carnosol (cell viabilities: 17.2% for 20[Formula: see text]μg/ml of CS vs. 100% for control, [Formula: see text]). Carnosol induced apoptosis and cell cycle arrest in a dose-dependent manner in MG-63 cells. Furthermore, carnosol exposure increased the levels of reactive oxygen species (ROS). The pre-treatment of NAC, the ROS scavenger, blocked the inhibition of cell viability in the carnosol treatment, indicating that ROS is important in the antiproliferation effect. Moreover, we demonstrated that carnosol significantly induced autophagy and co-administration of autophagy inhibitor reduced the antiproliferating effect of carnosol. This result exhibited the cytotoxic effect of autophagy induced by carnosol in MG-63 cells. Interestingly, the treatment of NAC decreased carnosol-induced autophagy. Collectively, these data indicate that carnosol suppresses the viability of human osteosarcoma MG-63 cells by upregulation of apoptosis and autophagy, which are both mediated by ROS. Thus, carnosol might serve as a potential therapeutic agent against osteosarcoma.

Topics: Abietanes; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; Autophagy; Cell Survival; Dose-Response Relationship, Drug; Humans; Osteosarcoma; Reactive Oxygen Species; Rosmarinus; Tumor Cells, Cultured