Description:
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 ER? 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 ER?, which showed clear synergistic effects on inhibiting the cell viability of MCF7 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 ER?, and it revealed its potential activity as an ER? 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.

URL:
http://103.158.96.210:88/web_repository/uploads/ps-28-76.pdf

Type:
Journal

Document:
Diploma III Farmasi

Date:
23-06-2024

Author:
Mohamed F. Elshal