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Pharm Sci. 2022;28(1): 76-85.
doi: 10.34172/PS.2021.22

Scopus ID: 85127089761
  Abstract View: 754
  PDF Download: 540

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 1 ORCID logo, Norhan Eid 1, Ibrahim El-Sayed 2, Wael El-Sayed 3, Ahmed Ali Al-Karmalawy 4* ORCID logo

1 Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute, University of Sadat City, Sadat City, Egypt.
2 Chemistry Department, Faculty of Science, Kafrelsheikh University, Egypt.
3 Genetics Department, Faculty of Agriculture, Beni-Suef University, Egypt.
4 Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, Egypt.
*Corresponding Author: Email: akarmalawy@horus.edu.eg

Abstract

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.

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Submitted: 02 Jan 2021
Revision: 20 Apr 2021
Accepted: 20 Apr 2021
ePublished: 26 Apr 2021
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