Ramazan Behzadi, Ahmad Hormati, Karim Eivaziatashbeik, Sajjad Ahmadpour*, Fatemeh Khodadust, Fatemeh Zaboli, Esmail Fattahi, Rana Jahanban-Esfahlan and Khaled Seidi Pages 1861 - 1870 ( 10 )
Background: Anti-cancer activity of some lactic acid bacterial strains is well documented in several 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: Anti-cancer effect 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 reduction in tumor weight and volume by both 24h and 48h supernatants (10 µg/ml and 20 µg/ml) after 15 days. According to the 99mTc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both 24h and 48h supernatant (20 µg/ml) led to 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.
Breast cancer, probiotics, MTT assay, histopathology, 99mTc-MIBI, biodistribution.
North Research Center, Pasteur Institute of Iran, Amol, Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Department of Orthopedics, Urmia University of Medical Sciences, Urmia, Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Department of Rheumatology, VU University Medical Center, Amsterdam, Department of Biology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Department of Biology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz