Qasem Zena, Pavlin Matic, Ritacco Ida, Avivi Matan Y, Meron Shelly, Hirsch Melanie, Shenberger Yulia, Gevorkyan-Airapetov Lada, Magistrato Alessandra, Ruthstein Sharon
Department of Chemistry and the Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat-Gan, Israel.
National Research Council of Italy (CNR)-Institute of Material (IOM) C/o International School for Advanced Studies (SISSA), Trieste, Italy.
Front Mol Biosci. 2022 Oct 10;9:1011294. doi: 10.3389/fmolb.2022.1011294. eCollection 2022.
Copper ions play a crucial role in various cellular biological processes. However, these copper ions can also lead to toxicity when their concentration is not controlled by a sophisticated copper-trafficking system. Copper dys-homeostasis has been linked to a variety of diseases, including neurodegeneration and cancer. Therefore, manipulating Cu-trafficking to trigger selective cancer cell death may be a viable strategy with therapeutic benefit. By exploiting combined and experimental strategies, we identified small peptides able to bind Atox1 and metal-binding domains 3-4 of ATP7B proteins. We found that these peptides reduced the proliferation of cancer cells owing to increased cellular copper ions concentration. These outcomes support the idea of harming copper trafficking as an opportunity for devising novel anti-cancer therapies.
铜离子在各种细胞生物学过程中发挥着关键作用。然而,当这些铜离子的浓度不受复杂的铜转运系统控制时,它们也会导致毒性。铜稳态失衡与多种疾病有关,包括神经退行性变和癌症。因此,操纵铜转运以触发选择性癌细胞死亡可能是一种具有治疗益处的可行策略。通过利用综合和实验策略,我们鉴定出了能够结合Atox1和ATP7B蛋白金属结合结构域3-4的小肽。我们发现这些肽由于细胞内铜离子浓度增加而降低了癌细胞的增殖。这些结果支持了破坏铜转运作为设计新型抗癌疗法的一个机会的观点。