Proteomic Analysis Revealed Underlying Biological Pathways Associated with Hormetic Response of Hormone- Positive Breast Cancer Cell Line Exposed to Low-Dose Flavonoid Mixture

Yıl 2021, Cilt: 80 Sayı: 2, 145 - 153, 17.12.2021

Mete Bora Tüzüner , Ayşe Begüm Ceviz

Öz

Objective: 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 flavonoids.

Anahtar Kelimeler

Flavonoids, breast cancer, hormesis, proteomics

Proje Numarası

22859

Kaynakça

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