Apoptotic effect of supernatant of pre-conditioned bone marrow-mesenchymal stem cell by nano-silymarin against melanoma

Silymarin has been used for years to treat various diseases, but its effectiveness has been limited due to low bioavailability and solubility. Nano-micelle delivery systems, a consistently practical approach, can enhance the solubility and bioavailability of silymarin. Mesenchymal stem cells (MSCs) are a type of multipotent cells that can be derived from various tissues, such as bone marrow and adipose tissue. These cells exhibit remarkable capacities, including the ability to migrate to tumor sites, the potential to differentiate into diverse cell types, antioxidant properties, and immunomodulatory activities. These characteristics make MSCs important regulators in determining the fate of tumors within the body. This research aimed to examine the potential of inducing apoptosis in melanoma cells by using the supernatant from exposing MSCs to nano-silymarin. Methods: Initially, mouse bone marrow-MSCs (BM-MSCs) were extracted and characterized with specific markers using flow cytometry technique to confirm their phenotype. Subsequently, various doses of nano-silymarin (۳ and ۶ µM) were treated with BM-MSCs for ۴۸ hours. Finally, the supernatant of these pre-conditioned cells was treated with B۱۶F۱۰ cells for ۴۸ hours, and Annexin V/PI markers were analyzed using flow cytometry. Results: The presence of specific surface markers of MSCs, including CD۹۰, CD۱۰۵, and CD۷۳, and the absence of specific markers of hematopoietic cells, including CD۳۴, CD۴۵, and CD۱۱b, on the surface of the extracted cell confirmed their nature. The flow cytometry assay of Annexin V/PI demonstrated that the ۳ µM concentration group resulted in ~۲۵% apoptosis of B۱۶F۱۰ cells, while the ۶ µM concentration group resulted in less than ۲۰% apoptosis. The percentage of apoptotic effect of both concentrations is significantly higher than the group of untreated MSCs. Conclusion: The increase in the percentage of B۱۶F۱۰ cell apoptosis in BM-MSCs groups treated with nano-silymarin showed that this substance has the ability to induce immunomodulatory and anticancer phenotype in BM-MSCs cells. However, molecular studies, as well as in vivo studies are recommended for a more accurate evaluation of this treatment.

کلیدواژه ها:

Bone marrow-mesenchymal stem cell ، nano-silymarin ، melanoma ، apoptosis