Lung cancer metastasis remains a significant challenge in cancer therapy, necessitating the exploration of novel treatment modalities. Silymarin, a natural compound derived from milk thistle, has demonstrated promising anticancer properties. This work explored the inhibitory effects of silymarin on lung cancer metastasis and revealed the underlying processes, focusing on matrix metalloproteinase (MMP) 2 and MMP-9 activities. Using a combination of in vitro and molecular docking analyses, we found that silymarin effectively reducing the lung cancer cells' motility and invasion by modulation of expression of MMP-2 and MMP-9. Furthermore, MTT assays revealed a dose-dependent inhibition of cell proliferation upon silymarin treatment and found the IC50 value at 58 μM. We observe that apoptotic morphology characteristic in silymarin treated groups. Cell cycle analysis exhibit the cell cycle arrest at G1 phase, 25.8 % increased apoptosis in silymarin treated groups, as evidenced by Annexin V staining. Moreover, silymarin treatment shows the lipid peroxidation in elevated level and reduced in enzymatic antioxidant level, indicating its potential role in mitigating oxidative stress induce cell death. Gelatin zymography assay indicates the silymarin has ability to inhibit the MMP-2 and MMP-9 expression in lung cancer. Additionally, cell migration assays and colony formation assays demonstrated impaired migratory and colony-forming abilities of lung cancer cells when treated with silymarin. Molecular docking studies further supported the binding affinity of silymarin with MMP-2 and MMP-9, demonstrate the −10.26 and −6.69 kcal/mol of binding energy. Collectively, our findings highlight the multifaceted anticancer properties of silymarin against lung cancer metastasis, providing insights into its therapeutic potential as an adjuvant treatment strategy.
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