Evaluation of Anti-Tumor Potential of Lactobacillus acidophilus ATCC4356 Culture Supernatants in MCF-7 Breast Cancer

Anticancer Agents Med Chem. 2021;21(14):1861-1870. doi: 10.2174/1871520621666201207085239.

Abstract

Background: The anti-cancer activity of some lactic acid bacterial strains is well documented in several kinds of literatures. Lactobacillus strains have received considerable attention as a beneficial microbiota. The aim of this study is to evaluate the effects of anti-tumor activities of L. acidophilus ATCC4356 culture supernatants on the MCF-7 human breast cancer cells.

Materials and methods: The anti-cancer effects of 24h and 48h culture supernatants at various concentrations (1.25, 2.5, 5, 10 and 20 μg/ml) were determined by various in vitro and in vivo assays including MTT, tumor volume measurement as well as 99mTc-MIBI biodistribution in MCF-7 tumor bearing nude mice and histopathology test. For evaluation of the related mechanism of action, quantitative PCR was conducted.

Results: The 48h culture supernatants at 10 and 20 μg/ml exhibited significant in vitro inhibition of MCF-7 cell proliferation. However, this inhibition was not observed for HUVEC human endothelial normal cells. Q-PCR indicated that treatment by the supernatant led to a significant downregulation of VEGFR (~ 0.009 fold) and Bcl- 2 (~ 0.5 fold) and upregulation of p53 (~ 1.3 fold). In vivo study using MCF-7 xenograft mouse models demonstrated a reduction in tumor weight and volume by both 24h and 48h supernatants (2 mg/kg) after 15 days. According to the 99mTc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both 24h and 48h supernatant (2mg/kg) led to a significant decrease in tumor uptake compared with the control group.

Conclusion: These results suggest that the culture supernatants of L. acidophilus ATCC4356 at suitable concentrations can be considered as a good alternative nutraceutical with promising therapeutic indexes for breast cancer.

Keywords: 99mTc-MIBI; Breast cancer; MTT assay; biodistribution.; histopathology; probiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Culture Media / chemistry
  • Culture Media / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Lactobacillus acidophilus / chemistry*
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Nude

Substances

  • Antineoplastic Agents
  • Culture Media