Induction of Cell Death by Bifidobacterium infantis DS1685 in Colorectal and Breast Cancers via SMAD4/TGF-Beta Activation

J Microbiol Biotechnol. 2024 Aug 28;34(8):1698-1704. doi: 10.4014/jmb.2404.04055. Epub 2024 Jul 12.

Abstract

Therapeutic advancements in treatments for cancer, a leading cause of mortality worldwide, have lagged behind the increasing incidence of this disease. There is a growing interest in multifaceted approaches for cancer treatment, such as chemotherapy, targeted therapy, and immunotherapy, but due to their low efficacy and severe side effects, there is a need for the development of new cancer therapies. Recently, the human microbiome, which is comprised of various microorganisms, has emerged as an important research field due to its potential impact on cancer treatment. Among these microorganisms, Bifidobacterium infantis has been shown to significantly improve the efficacy of various anticancer drugs. However, research on the role of B. infantis in cancer treatment remains insufficient. Thus, in this study, we explored the anticancer effect of treatment with B. infantis DS1685 supernatant (BI sup) in colorectal and breast cancer cell lines. Treatment with BI sup induced SMAD4 expression to suppress cell growth in colon and breast cancer cells. Furthermore, a decrease in tumor cohesion was observed through the disruption of the regulation of EMT-related genes by BI sup in 3D spheroid models. Based on these findings, we anticipate that BI sup could play an adjunctive role in cancer therapy, and future cotreatment of BI sup with various anticancer drugs may lead to synergistic effects in cancer treatment.

Keywords: B. infantis DS1685 supernatant; SMAD4; TGF-beta; breast cancer; colorectal cancer.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Bifidobacterium longum subspecies infantis* / genetics
  • Bifidobacterium longum subspecies infantis* / metabolism
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms* / microbiology
  • Colorectal Neoplasms* / pathology
  • Female
  • Humans
  • Probiotics
  • Smad4 Protein* / genetics
  • Smad4 Protein* / metabolism
  • Transforming Growth Factor beta* / metabolism

Substances

  • Smad4 Protein
  • Transforming Growth Factor beta
  • SMAD4 protein, human
  • Antineoplastic Agents