The secondary metabolites produced by Lactobacillus plantarum downregulate BCL-2 and BUFFY genes on breast cancer cell line and model organism Drosophila melanogaster: molecular docking approach

Cancer Chemother Pharmacol. 2020 Jan;85(1):33-45. doi: 10.1007/s00280-019-03978-0. Epub 2019 Oct 31.

Abstract

Purpose: The current study was designed to evaluate the toxicity of the secondary metabolites of Lactobacillus plantarum against the human breast cancer cell line (MCF-7) and the Drosophila melanogaster.

Methods: In this study, toxicity analyses of secondary metabolites of Lactobacillus plantarum were analyzed on breast cancer cells, and the Drosophila melanogaster. After application, in the MCF-7 cell line, expression levels of RRAS-2, TP53, BCL-2, APAF-1, CASP-3, FADD, CASP-7, BOK genes; in D. melanogaster; expression levels of RAS64B P53, BUFFY, DARK, DECAY, FADD, DRICE, and DEBCL genes were determined by RT-PCR. In addition, analysis of L. plantarum secondary metabolite was performed by GC-MS method and molecular binding poses of secondary metabolites and human enzymes were investigated in silico.

Results: Drosophila melanogaster being used as a model organism where some of the human genes were preserved. The IC50 value of the secondary metabolite in the MCF-7 cell line was determined to be 0.0011 mg/ml. Lethal concentration 50 (LC50) and 99 (LC99) values of secondary metabolites against fruit fly adults were 0.24 mg/ml and 0.54 mg/ml, respectively. The expression levels of BCL-2 and BUFFY genes which are anti-apoptotic in human and fruit flies have been reduced, and at the same time, increased expression of DECAY, FADD, RAS64B apoptotic genes in D. melanogaster.

Conclusion: The substance detected in the secondary metabolite content and encoded as L13 (3-phenyl-1, 2, 4-benzotriazine) has been observed to have high binding affinity in the studied genes.

Keywords: Apoptosis; Drosophila melanogaster; Gene expression; Lactobacillus plantarum; MCF-7; Molecular docking.

MeSH terms

  • Animals
  • Apoptosis
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / microbiology
  • Breast Neoplasms / pathology*
  • Cell Proliferation
  • Cytotoxins / pharmacology
  • Drosophila Proteins / antagonists & inhibitors*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / microbiology
  • Female
  • Gene Expression Regulation / drug effects*
  • Humans
  • Lactobacillus plantarum / metabolism*
  • MCF-7 Cells
  • Metabolome*
  • Models, Animal
  • Molecular Docking Simulation
  • Probiotics / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*

Substances

  • Buffy protein, Drosophila
  • Cytotoxins
  • Drosophila Proteins
  • Proto-Oncogene Proteins c-bcl-2