Syringin as TGF-βR1, HER2, EGFR, FGFR4 Kinase, and MMP-2 Inhibitor and Potential Cytotoxic Agent against ER+ Breast Cancer Cells

Background: Breast cancer is currently the most diagnosed cancer worldwide. Neoplastic cells and components of the tumor microenvironment trigger enzymes and receptors to facilitate cancer advancement. Syringin, a natural phenylpropanoid glycoside, has been reported to possess anti-cancer activity and affinity with numerous druggable targets of breast carcinoma. Objectives: This work aims to evaluate the effects of syringin on the growth of breast cancer cells (MCF-7) and normal dermal fibroblast cells (HDFn) and its ability to inhibit the protein targets of breast cancer. Methods: Syringin was investigated on cell lines in vitro via MTT assay. Using non-cell-based activity assay kits, its influence on the activity of transforming growth factor-beta receptor type 1 (TGF-βR1), human epidermal growth factor receptor (HER2), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor 4 (FGFR4), and matrix metalloproteinase-2 (MMP-2) was evaluated. Results: Syringin exhibited significant cytotoxicity against MCF-7 cells (IC50: 32.11 μM for 24 hours and 21.35 μM for 48 hours) and was non-toxic on healthy HDFn cells (IC50: >100 μM for 24 and 48 hours). It significantly suppressed the activity of cancer and angiogenesis regulating enzymes in vitro with commendable IC50 values on TGF-βR1 kinase (IC50: 6.48 μM), HER2 kinase (IC50: 7.18 μM), EGFR kinase (IC50: 12.38 μM), FGFR4 kinase (IC50: 16.03 μM), and MMP-2 (IC50: 16.07 μM). Conclusion: Findings showed the selective toxicity of syringin on breast cancer cells and its potential against pro-angiogenic enzymes. These discoveries strongly indicate the significance and therapeutic potential of syringin in targeted cancer therapy.