In vitro and In vivo effects of Cucumis melo seeds extract and its purified trypsin inhibitor on angiogenesis and tumor characteristics in balb-c mice with breast cancer in comparison with tamoxifen

Abstract Background: Melon seeds as an excellent supply of protease inhibitors may have a protective role against tumor progression and angiogenesis. However, its anti-angiogenesis effects and related mechanism of action during cancer progression remain elusive. This study aimed to investigate the impact of bioactive compounds of melon seed on the expression of angiogenesis genes in breast cancer cell lines.Methods: Trypsin inhibitor (TI) was purified from the seed powder of Cucumis melo (Muskmelon) Half-maximal inhibitory concentration (IC50) was determined for TI, extract of melon seed powder (EXT), and tamoxifen (TAM) by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Breast tumor was induced by subcutaneous injection of MC4-L2 cell line in blab-c inbreed mice breast tissue. After tumor growth, mice were treated with TI, EXT, and TAM in different doses and combinations to examine their effects on the tumor characteristics and the expression of angiogenesis-related genes including MMP-2, MMP-9, and VEGF using the RT-PCR method.Results: TI, EXT, TAM, and adjuvant treatment of TI+TAM resulted in a reduction in expression of MMP-2, MMP-9, and VEGF. All treatments improved breast tumor characteristics and necrosis. The RT-PCR method verified the positive effects of treatments on breast cancer cell lines and tumors.Conclusion: The results indicated that trypsin Inhibitor Purified from Cucumis melo seeds alone and in combination with tamoxifen might be a potential therapy with beneficial anti-angiogenesis and anti-tumor effects in breast cancer. Further studies are warranted.