Silymarin induces multiple myeloma cell apoptosis by inhibiting the JAK2/STAT3 signaling pathway

Multiple myeloma (MM) is a malignant tumor that originates in the plasma cells of the bone marrow, interfering with the production of healthy blood cells and causing notable damage to bones and Other tissues. Currently, the treatment options for MM are limited and often fail to provide effective and well-tolerated solutions. Silymarin, a primary active compound found in the dried fruit of Silybum marianum, is known for its inhibitory action on lipoxygenases and peroxidases. In addition to its known benefits in reducing liver toxicity and enhancing radiation protection, silymarin has shown promise in lowering lipid levels. Silymarin has Anticancer properties; however, the specific mechanisms and efficacy of silymarin in treating MM require further investigation. In the present study, network pharmacology was employed to discern the targets and associated pathways of silymarin against MM. The cytotoxic effects of silymarin on MM were subsequently tested using RPMI 8226 and H929 cell lines. Furthermore, the molecular targets of silymarin in MM were assessed through immunofluorescence, reverse transcription-quantitative polymerase chain reaction and molecular docking studies. A total of 15 notable targets of silymarin associated with MM were identified, along with 60 interactions among these targets and several associated signaling pathways. In vitro experiments using Cell Counting Kit-8 and flow cytometry revealed that silymarin markedly promoted Apoptosis in MM cells. Additionally, there was a reduction in the expression of anti-apoptotic genes, such as Bcl-2 and Bcl-xL. After silymarin treatment, a decrease in phosphorylation of JAK2 and STAT3 was observed in MM cells, and it was suggested that silymarin potentially binds to JAK2 and STAT3. In conclusion, silymarin was revealed to trigger Apoptosis in MM cells by blocking the JAK2/STAT3 signaling pathway. This mechanism highlights the potential of silymarin as a therapeutic agent that can target specific molecular pathways to combat MM.

JAK2/STAT3 signaling pathway; apoptosis; molecular docking; multiple myeloma; network pharmacology; silymarin.