Auranofin sensitizes breast cancer cells to paclitaxel mediated cell death via regulating FOXO3/Nrf2/Keap1 signaling pathway.
N DeepikaNagarajan Rajendra PrasadT RadhigaPublished in: Cell biochemistry and function (2024)
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor which acts as a regulator for cellular oxidative stress, and tightly regulated by Kelch-like ECH-associated protein 1 (Keap1). In this study, we found that auranofin and paclitaxel combination treatment increased TUNEL positive apoptotic cells and enhanced the DNA damage marker γ-H2AX in MCF-7 and MDA-MB-231 breast cancer cells. The immunoblotting analysis revealed the combination of auranofin and paclitaxel significantly increased the FOXO3 expression in a concentration dependent manner. Further we observed that auranofin and paclitaxel treatment prevents the translocation of Nrf2 in a concentration dependent manner. The increased FOXO3 expression might be involved in the cytoplasmic degradation of Nrf1-Keap1 complex. Further, the molecular docking results confirm auranofin act as the agonist for Foxo3. Therefore, the present results suggest that auranofin sensitize the breast cancer cells to paclitaxel via regulating FOXO3/Nrf2/Keap1signaling pathway.
Keyphrases
- breast cancer cells
- oxidative stress
- signaling pathway
- induced apoptosis
- pi k akt
- transcription factor
- cell cycle arrest
- dna damage
- cell death
- molecular docking
- nuclear factor
- poor prognosis
- ischemia reperfusion injury
- diabetic rats
- epithelial mesenchymal transition
- protein protein
- toll like receptor
- cell proliferation
- gene expression
- chemotherapy induced
- endoplasmic reticulum stress
- heat shock
- long non coding rna
- combination therapy
- binding protein
- dna repair
- mouse model