Effect of Silibinin on the Expression of Mir-20b, Bcl2L11, and Erbb2 in Breast Cancer Cell Lines

Mol Biotechnol. 2023 Dec;65(12):1979-1990. doi: 10.1007/s12033-023-00702-5. Epub 2023 Mar 11.

Abstract

This study aimed to evaluate the comparative effect of silibinin (SB) on the expression of MiR‑20b and BCL2L11 in T47D and MCF-7 cell lines. Molecular simulation studies were carried out to analyze Erbb2, as a potential target of SB, to direct the breast cancer cells toward apoptosis. At first, cell viability, apoptosis, and cell cycle arrest-inducing capacity of SB were examined using MTT and flow cytometry analysis, respectively. Real-time PCR (RT-PCR) was employed to assess the effect of SB on BCL2L11, Phosphatase and tensin homolog (PTEN), and Caspase 9 mRNarrest-indu. Moreover, alterations in Caspase 9 protein expression were determined using Western blot analysis. Finally, AutoDockVina software was used to dock the SB/ MiR‑20b and SB/ erb-b2 receptor tyrosine kinase 2 (Erbb2) interaction. The obtained data revealed the potent cytotoxicity of SB in both T47D and MCF-7 cells through apoptosis induction and cell cycle arrest. SB-treated cells also showed downregulation of MiR‑20b and high expression of BCL2L11, PTEN, and Caspase 9 mRNA compared to non-treated cancer cells. Computational docking showed a strong interaction between SB/ MiR‑20b and SB/Erbb2. It can be concluded that SB had a strong anti-tumorigenic activity through BCL2L11upregulation and MiR‑20b down expression, maybe through targeting the PTEN and interacting with Erbb2, which resulted in apoptotic induction and cell cycle arrest.

Keywords: Apoptosis; Breast cancer; MiR‑20b; Molecular docking; Silibinin.

MeSH terms

  • Apoptosis
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Caspase 9 / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • MCF-7 Cells
  • MicroRNAs* / genetics
  • Receptor, ErbB-2 / genetics
  • Silybin / pharmacology

Substances

  • Silybin
  • Caspase 9
  • Receptor, ErbB-2
  • MicroRNAs