Inhibitory effects of Lactobacilli cocktail on HT-29 colon carcinoma cells growth and modulation of the Notch and Wnt/β-catenin signaling pathways

Microb Pathog. 2020 Feb:139:103829. doi: 10.1016/j.micpath.2019.103829. Epub 2019 Nov 2.

Abstract

Probiotics could be considered as attractive candidates for preventing tumor growth through maintaining homeostasis. The aim of this study was to evaluate the inhibitory effect of a cocktail of five Lactobacillus species on human colorectal carcinoma cell line HT-29. The anti-proliferative and apoptotic effects of Lactobacilli cocktail were evaluated using MTT and flow cytometry tests, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to analyze the expression of several genes in the Notch (notch, hes1, msi1, and numb) and Wnt/β-catenin (CTNNB1 and CCND1) pathways, following the treatment of HT-29 cells with Lactobacilli cocktail. The treatment by Lactobacilli cocktail induced a significant anti-proliferative effect and late stage apoptosis among the cancer cells (p < 0.05). Compared to the untreated cells, Lactobacilli cocktail induced the down-regulation of notch, hes1, and msi1 genes and up-regulation of numb gene in the Notch pathway as well as the down-regulation of CTNNB1 and CCND1 genes in the Wnt/β-catenin pathway in a time-dependent manner (p < 0.05). CONCLUSION: Lactobacilli cocktail was shown to have beneficial anti-tumor effects on HT-29 cells by modulating the Notch and Wnt/β-catenin pathways; therefore, the use of Lactobacilli probiotics as nutritional supplements may prevent the incidence of colon cancer.

Keywords: Anti-proliferation; Apoptosis; Lactobacilli; Notch; Wnt/β-catenin.

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Gene Expression Regulation, Bacterial
  • HT29 Cells
  • Humans
  • Lactobacillus / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Signal Transduction*
  • Transcription Factor HES-1 / genetics
  • Transcription Factor HES-1 / metabolism
  • Wnt Signaling Pathway*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • CCND1 protein, human
  • CTNNB1 protein, human
  • MSI1 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • NUMB protein, human
  • RNA-Binding Proteins
  • Transcription Factor HES-1
  • beta Catenin
  • Cyclin D1
  • HES1 protein, human