NAF-1 44-67 is derived from the transmembrane and flexible loop regions of the human mitochondrial/ER membrane-anchored NEET protein, Nutrient Autophagy Factor 1 (NAF-1), with d amino acid residues incorporated into its sequence to improve stability in biological systems. NAF-1 44-67 selectively permeates through the plasma membranes of human epithelial breast cancer cells and targets their mitochondria and ER, triggering cell death with characteristics of apoptosis, ferroptosis and necroptosis. The specificity of NAF-1 44-67 towards cancer cells is due to it being derived from the NAF-1 sequence that resides in the mitochondrial and ER membranes. In vivo NAF-1 44-67 significantly decreases tumour growth in xenograft mice carrying human triple-negative breast cancer MDA-MB-231 tumours.
