concanavalin-a shows synergistic cytotoxicity with tamoxifen via inducing apoptosis in estrogen receptor-positive breast cancer: in vitro and molecular docking studies

Background: tamoxifen (tam) is the main treatment of estrogen receptor (er)-positive breast cancer, however; its adverse effects and development of resistance hinder its use. concanavalin a (con a) is a mannose/glucose-binding lectin that has been reported to induce apoptosis in a variety of cell lines. methods: the effects of con a on tam-induced cell death in erα positive cell line (mcf-7) were elucidated to identify the potential underlying molecular mechanisms using in silico (molecular docking) and in vitro (cytotoxicity assay, cell cycle analysis, annexin v-fitc apoptosis assay, and reverse transcription and quantitative real time-pcr) techniques as well. results: the results demonstrated that combined treatment with con a and tam reduced the expression of erα, which showed clear synergistic effects on inhibiting the cell viability of mcf- 7 cells. interestingly, the combined treatment induces g1 phase arrest and reduces cyclin d1 activity while increasing apoptosis and autophagy as indicated by decreasing the expression level of anti-apoptosis gene bcl-2 and increased apoptosis/autophagic gene bnip3. molecular docking was conducted to evaluate the binding affinity of con a towards erα, and it revealed its potential activity as an erα antagonist. our data further indicated that con a administration increased the drug reduction index of tam. conclusion: overall, our findings suggested that con a could be used as an adjuvant agent with tam to improve its effectiveness as an anticancer agent.