Author/Authors :
Esfandiary، Ali نويسنده Department of Medical Genetics, Shahid Beheshti University
of Medical Sciences, Tehran, IR Iran , , Taherian-Esfahani، Zahra نويسنده Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran , , Abedin-Do، Atieh نويسنده Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran , , Mirfakhraie، Reza نويسنده Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mirfakhraie, Reza , Shirzad، Mahdieh نويسنده Department of Microbiology, School of Biology and Center of Excellence in Phylogeny Living Organisms, College of Science, University of Tehran, Tehran, Iran , , Ghafouri-Fard، Soudeh نويسنده , , Motevaseli، Elahe نويسنده Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran ,
Abstract :
Objective: Hypoxia-Inducible Factor (HIF)-1 plays an essential role in the body’s response to
low oxygen concentrations and regulates expression of several genes implicated in homeostasis,
vascularization, anaerobic metabolism as well as immunological responses. Increased
levels of HIF-1? are associated with increased proliferation and more aggressive breast tumor
development. Lactobacilli have been shown to exert anti-cancer effects on several malignancies
including breast cancer. However, the exact mechanism of such effect is not clear yet.
The aim of this study was to analyze the expression of selected genes from HIF pathway in a triple
negative breast cancer cell line (expressing no estrogen and progesterone receptors as well
as HER-2/Neu), MDA-MB-231, following treatment with two lactobacilli culture supernatants.
Materials and Methods: In this experimental study, we analyzed the expression of HIF-
1?, SLC2A1, VHL, HSP90, XBP1 and SHARP1 genes from HIF pathway in MDA-MB-231
cells, before and after treatment with Lactobacillus crispatus and Lactobacillus rhamnosus
culture supernatants (LCS and LRS, respectively) by means of quantitative reverse-transcription
polymerase chain reaction (qRT-PCR).
Results: Both LRS and LCS had cytotoxic effects on MDA-MB-231 cells, while the former
type was more cytotoxic. LRS dramatically down-regulated expression levels of the HIF-
1?, HSP90 and SLC2A1 in the MDA-MB-231 cells. LCS had similar effect on the expression
of HSP90, to what was observed in the LRS treatment. The expression level of tumor
suppressor genes VHL and SHARP1 were also decreased in LCS treated cells.
Conclusion: Although both LCS and LRS had cytotoxic effects on the MDA-MB-231 cells,
it is proposed that LRS could be more appropriate for pathway directed treatment modalities,
as it did not decrease expression of tumor suppressor genes involved in HIF pathway.
Down-regulation of HIF pathway mediated oncogenes by LRS suggests that the cytotoxic
effects of this lactobacillus may at least be partly caused by this mechanism. As previous
studies have shown that inhibition of HIF-1? and HSP90 expressions have therapeutic
impact on cancer treatment, the inhibitory effect of LRS on expression of these genes
implies that this lactobacillus can be used in treatment strategies.
