Marine Algae as Source of Bioactive Compounds: Efficacy on Human Osteoarticular Cells

Marine algae have been demonstrated to be strong candidates for the extraction and enforcement of novel drugs and in recent years, significant development has been achieved in the isolation of these active compounds with several activities, such as anticancer, anti-inflammation, antioxidant, and having an inhibitory effect on ROS generation. Reports relevant to the chemical properties of brown algae Padina sp. are limited and those accompanied to a comprehensive evaluation of the biological activity on osteosarcoma (OS) are non-existent. We explored the chemical composition of French Polynesian Padina pavonica extract (EPP) by spectrophotometric assays (total phenolic, flavonoid and tannin content, and antioxidant activity) and by GC-MS analysis, and provided EPP lipid and sterols profiles. Several compounds with relevant biological activity were identified suggesting interesting pharmacological and health-protecting effects for EPP. Moreover, we demonstrated that EPP presents good anti-proliferative and pro-apoptotic activities against two OS cell lines, SaOS-2 and MNNG, with different cancer-related phenotypes. Finally, our data suggest that EPP might target different properties associated with cancer development and aggressiveness. The pro-osteogenic ability of Padina pavonica extract on human primary osteoblast (HOb) was investigated, as well. Our data indicated that EPP is a safe product as it did not show any effect on osteoblast viability. EPP showed to possess a beneficial effect on HOb functionality, triggering their differentiation (increase in the expression of both earlier and late differentiation stage markers) and mineralization abilities. Therefore, EPP showed a significant capability of promoting osteoblast phenotype. Given its positive effect on bone homeostasis, EPP could be used as a useful nutraceutical product that, in addition to a healthy lifestyle and diet, can be able to contrast and prevent bone diseases, especially those connected with ageing, such as osteoporosis (OP). Accordingly, we focused on the transfer of these results on a human osteosarcoma cell line, SaOS-2, with the aim to set up an experimental model for the screening of natural compounds. Our experiments proved once again the non-cytotoxic effect of EPP on SaOS-2 cells. EPP showed to stimulate the expression of ALPL, a marker of the early stage of osteoblast differentiation, while the increase in collagen deposition did not appear significant compared to the control cell culture. Lastly, a significant increase in matrix mineralization by SaOS-2 EPP-treated cells was detected. These experiments have confirmed the positive effects of EPP in the physiological metabolism of bone tissue. However, results were not superimposable with the one obtained in primary human osteoblasts in terms of entity of the increase in the expression of bone differentiation and functionality markers (ALPL activity and mineralized nodules deposition). Therefore, the identification and selection of more proper cell culture conditions for the study of EPP as a pro-osteogenic agent on osteoblast-like cell model, such as SaOS-2 cells, might be a future perspective of our research group. Lastly, the potential protective effect of EPP against damages induced by oxidative stress was investigated through proteomic and redox proteomic analysis. EPP demonstrated the ability to modulate the expression of several proteins belonging to different functional groups including those involved in stress response in both the experimental conditions (long-term cell cultures and H2O2-induced oxidative stress). Moreover, the analysis of carbonylated proteins in long-term cell cultures revealed that EPP possess a significant ability in protecting proteins from oxidation. A lower protective effect against protein oxidation in H2O2-induced oxidative stress was detected. Therefore, Padina pavonica demonstrated to be a valuable and rich source of bioactive molecules that might be useful, together with a proper diet and lifestyle, in the prevention and treatment of pathologies associated with oxidative stress, such as OP, or in physiological ageing, so that EPP might be used in an anti-osteoporotic and anti-ageing context