Abstract View: 90

Research Article

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

Mohamed Elshal ORCID logo, Norhan Eid, Ibrahim El-Sayed, Wael El-Sayed, Ahmed Ali Al-Karmalawy* ORCID logo


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: Therefore, we aimed to elucidate the effects of Con A on TAM-induced cell death in ERα positive cell line (MCF-7) and to identify the potential underlying molecular mechanisms using in silico and in vitro techniques.
Results: Our 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 while minimizing its side effects.
Keywords: Lectins, Tamoxifen, Chemoresistance, MCF-7, Apoptosis, Combination therapy
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Submitted: 02 Jan 2021
Revision: 20 Apr 2021
Accepted: 20 Apr 2021
ePublished: 26 Apr 2021
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