Onco-Stem Cell Research Laboratory, Department of Biochemistry and Bioinformatics, Institute of Science, GITAM Deemed to be University, Visakhapatnam 530045, India.
CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500007, India.
Molecules. 2022 May 7;27(9):3011. doi: 10.3390/molecules27093011.
Iron is a crucial element required for the proper functioning of the body. For instance, hemoglobin is the vital component in the blood that delivers oxygen to various parts of the body. The heme protein present in hemoglobin comprises iron in the form of a ferrous state which regulates oxygen delivery. Excess iron in the body is stored as ferritin and would be utilized under iron-deficient conditions. Surprisingly, cancer cells as well as cancer stem cells have elevated ferritin levels suggesting that iron plays a vital role in protecting these cells. However, apart from the cytoprotective role iron also has the potential to induce cell death via ferroptosis which is a non-apoptotic cell death dependent on iron reserves. Apoptosis a caspase-dependent cell death mechanism is effective on cancer cells however little is known about its impact on cancer stem cell death. This paper focuses on the molecular characteristics of apoptosis and ferroptosis and the importance of switching to ferroptosis to target cancer stem cells death thereby preventing cancer relapse. To the best of our knowledge, this is the first review to demonstrate the importance of intracellular iron in regulating the switching of tumor cells and therapy resistant CSCs from apoptosis to ferroptosis.
铁是人体正常运作所必需的关键元素。例如，血红蛋白是血液中输送氧气到身体各个部位的重要成分。血红蛋白中存在的血红素蛋白以亚铁状态形式包含铁，这种亚铁状态调节氧气输送。体内多余的铁以铁蛋白的形式储存，并在缺铁条件下被利用。令人惊讶的是，癌细胞和癌症干细胞的铁蛋白水平升高，这表明铁在保护这些细胞方面起着至关重要的作用。然而，除了细胞保护作用外，铁还有可能通过铁死亡诱导细胞死亡，铁死亡是一种依赖铁储备的非凋亡性细胞死亡。细胞凋亡是一种依赖半胱氨酸天冬氨酸蛋白酶的细胞死亡机制，对癌细胞有效，但对其对癌症干细胞死亡的影响知之甚少。本文重点介绍了细胞凋亡和铁死亡的分子特征，以及切换到铁死亡以靶向癌症干细胞死亡从而预防癌症复发的重要性。据我们所知，这是第一篇证明细胞内铁在调节肿瘤细胞和治疗耐药性 CSCs 从细胞凋亡向铁死亡转换中的重要性的综述。
