Lactobacilli modulate hypoxia-inducible factor (HIF)-1 regulatory pathway in triple negative breast cancer cell line

Background: Hypoxia-Inducible Factor (HIF)-1 plays an essential role in the body s response to low oxygen concentrations .Increased levels of HIF-1α are associated with increased proliferation and more aggressive breast tumors. Lactobacilli have been shown to exert anti-cancer effects on several cancers including breast cancer. However, the exact mechanism of such effect is not clarified yet. In this study we analyzed the expression of selected genes from HIF Pathway in MDA-MB-231 cells by following treatment with two Lactobacilli culture supernatants. Material and methods: In this experimental study, we analyzed the expression of HIF-1α, SLC2A1, VHL, HSP90, XBP1 and SHARP1 genes from HIF pathway in MDAMB- 231 cells before and after treatment with Lactobacillus crispatus and Lactobacillus rhamnosus culture supernatants (LCS and LRS, respectively) by means of quantitative real time PCR. Results: Both LRS and LCS had cytotoxic effects on MDA-MB-231 cells with the former being more cytotoxic. LRS dramatically down regulated the expressions of HIF-1α, HSP90 and SLC2A1 in MDA-MB-231 cells. LCS had the similar effect on the expression of HSP90 as LRS. However, LCS also decreased the expression of tumor suppressor genes VHL and SHARP1. Conclusions: Although both LCS and LRS had cytotoxic effects on MDA-MB-231 cells, LRS seems to be more appropriate for pathway directed treatment modalities as it did not decrease expression of tumor suppressor genes from this pathway. As previous studies have shown that inhibition of HIF-1α and HSP90 expressions have therapeutic value in cancer treatment, inhibitory effect of LRS on their expression may be of significance.

Keywords:

breast cancer , lactobacillus , HIF