الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
Breast cancer (BC) is the most commonly occurring cancer in women in Egypt, second only to liver cancer. Nutrient-Deprivation autophagy factor1 (NAF1), is 2Fe-2S cluster immune-detected protein in the outer mitochondrial membranes (OMM) and endoplasmic reticulum (ER). It is emerging as a key modulator in various cellular functions including the regulation of apoptosis and/or autophagy pathways, Ca2+ metabolism, and mediating Fe/Fe-S and/or ROS homeostasis.Pioglitazone (Pio) and curcumin (Cur) are potent anticancer agents. Pioglitazone exhibits its anticancer roles through several mechanisms, including cell cycle progression modulation, induction of apoptosis, and inhibition of invasion and metastasis. Curcumin exerts several anticancer mechanisms including cell proliferation inhibition, induction of apoptosis, reduction of angiogenesis, and mitigation of invasion and metastasis. Nevertheless, the molecular mechanism underlying the effects of using combined doses of Cur and/or Pio on NAF1 remains unclear.In this study, we aimed to investigate the possible anticancer activities of combined doses of Pio and Cur on highly expressed NAF1 and other signaling pathways implicated in BC including NRF2, p53, and APE1 pathways in human epithelial breast cancer cell line MCF-7. The nuclearregulator factor erythroid 2-related factor (NRF2) is a transcriptional factor control cellular defense against oxidative stress and inflammation. APE1 is a multifunctional protein involved in both the base excision repair (BER) pathway and redox signaling through modulating the transcriptional activity of several transcriptional factors including NRF2 and NF-ₖB. Anticancer effects for Cur and Pio on MCF-7 cells were determined using MTT Assay, Trypan blue Assay, Real-Time PCR for genes responsible for ROS detoxification, apoptotic, antiapoptotic, and inflammatory genes including NAF1, NRF2, KEAP1, HO1, NQO1, MDM2, p21, p53, BCL2, BAX, APE1, NF-ₖB,COX2, and IL6, ELISA for NRF2, p53, p21, and NF-ₖB proteins, and measuring of total cellular antioxidant capacity, superoxide dismutase and catalase activities.