Effect of milk fermented with a Lactobacillus helveticus R389(+) proteolytic strain on the immune system and on the growth of 4T1 breast cancer cells in mice

FEMS Immunol Med Microbiol. 2006 Jul;47(2):242-53. doi: 10.1111/j.1574-695X.2006.00088.x.


Previous studies on a murine model have demonstrated that the administration of Lactobacillus helveticus and Lactobacillus casei inhibits the development of fibrosarcoma and colon carcinoma, respectively. The aim of this work was to study the beneficial effects of the consumption of milk fermented by L. helveticus on a murine model for mammary carcinoma. Female BALB/c mice were challenged by a single subcutaneous injection of tumoral cells (American Type Culture Collection 4T1) in the left mammary gland. Prior to tumour injection, mice were fed for two, five or seven consecutive days with fermented milk. The following factors were monitored for 2 months: rate of tumour development, histological studies, apoptosis, phagocytic index, peritoneal macrophages, determination of beta-glucuronidase enzyme in peritoneal macrophages, determination of gamma-interferon (INFgamma) and tumour necrosis factor-alpha (TNF-alpha) in blood serum, determination of CD4+, CD8+, interleukin-6 (IL-6), IL-10, TNF-alpha and INFgamma by immunoperoxidase, and measurement of beta-glucuronidase activity in intestinal fluid. The administration of L. helveticus delayed the development of the tumour in all cases, a 2- or 7-day feeding period being most effective. This work demonstrates that milk fermented with L. helveticus decreases the growth rate of mammary tumours. The effect was mediated by increased apoptosis and decreased production of pro-inflammatory cytokines, in particular IL-6, implicated in oestrogen synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Growth Processes / immunology
  • Cultured Milk Products / immunology*
  • Cultured Milk Products / microbiology
  • Cytokines / immunology
  • Female
  • Glucuronidase / metabolism
  • Lactobacillus helveticus / enzymology
  • Lactobacillus helveticus / immunology*
  • Lactobacillus helveticus / metabolism
  • Macrophages, Peritoneal / immunology
  • Mice
  • Mice, Inbred BALB C
  • Peptide Hydrolases / metabolism
  • Phagocytosis / physiology


  • Cytokines
  • Glucuronidase
  • Peptide Hydrolases