+1 (202) 780-3397Mini Review - Asian Journal of Biomedical and Pharmaceutical Sciences (2023) Volume 13, Issue 101
Iron-Sulfur cluster and cancer related diseases
Iron-sulfur (Fe-S) clusters are essential protein cofactors involved in various cellular processes. Defects in Fe-S cluster biogenesis can lead to diseases like cancer. The stability and transfer of Fe-S clusters mediated by proteins like NAF-1 regulate cellular resistance to oxidative stress. This study examined how modulating NAF-1 and Fe-S cluster stability affected breast cancer tumor growth in MDA-MB-231 cells. Overexpression of NAF-1 enhanced antioxidant capacity and oxidative stress resistance, increasing tumor volume 3-fold. In contrast, a stabilizing mutation in NAF-1 inhibited cluster transfer to recipient proteins, decreasing antioxidant capacity and reducing tumor volume by 30%. The drug pioglitazone had similar effects to the NAF-1 mutation, hyperstabilizing its Fe-S cluster and suppressing its function. High cancer cell metabolism produces reactive oxygen species that are normally detoxified. New cancer therapies exploit this by overloading cells with oxidative radicals using iron nano-catalysts. Thus, understanding factors regulating Fe-S cluster stability in cancer cells provides opportunities to enhance prooxidant cancer therapies. Overall, this study demonstrated that increased Fe-S cluster stability reduces NAF-1 mediated antioxidant capacity and cancer cell growth, while destabilization enhances sensitivity to oxidative stress. Modulating proteins involved in Fe-S cluster transfer represents a potential therapeutic approach for cancer treatment.
Author(s): Mohammad Deylam Kamar