Tuzuner, Mete BoraCeviz, Ayşe Begüm2022-04-192022-04-192021Tüzüner, M. B. & Ceviz, A. B. (2021). Proteomic analysis revealed underlying biological pathways associated with hormetic response of hormone- positive breast cancer cell line exposed to low-dose flavonoid mixture. European Journal of Biology, 80(2), 145-153. https://doi.org/10.26650/EurJBiol.2021.1017807https://doi.org/10.26650/EurJBiol.2021.1017807https://hdl.handle.net/20.500.13055/212Objective: A considerable level of evidence has accumulated about the breast cancer risk-reducing effect of consuming specific flavonoids, through the increasing amount of research and epidemiologic studies. Different flavonoids may have different cellular bioavailability and favor, i.e., the occurrence of a hormetic effect, thus it is important to evaluate breast cancer cells’ response to different doses of flavonoids. This study aims to investigate the alterations of the biological pathways in a hormone-positive (HR+) breast cancer cell line as a resemblance for the most common breast cancer subtype, related to the low-dose exposure of the flavonoids. Materials and Methods: Different levels of doses were applied to MCF-7 breast cancer cells. In order to determine cellular proliferation, WST-1 analysis was conducted. The highest proliferation was observed with cell lines exposed to a low-dose flavonoid mixture and these were selected for further analysis. Intracellular protein expression were investigated by peptide analysis on a nano LC-MS/MS platform. A protein-protein interaction network and pathway analysis were conducted for the proteins expressed differently between the groups. Results: A total of 214 proteins were identified and 36 proteins with significant alterations (≥1.2-fold change, p≤0.05) were detected. Significant changes were observed in the pathways related to carbon metabolism, amino acid biosynthesis, splicing mechanism, mitochondrial protein import and translation elongation pathways. Conclusion: Our study demonstrated that flavonoids can have a hormetic effect which can initially alter metabolic pathways vital for cell proliferation and survival. These pathways may include potential targets for enhancing the anticancer activity of the flavonoidseninfo:eu-repo/semantics/openAccessFlavonoidsBreast cancerHormesisProteomicsArticle10.26650/EurJBiol.2021.10178078021451532-s2.0-85127704707Q4507424