Role of Intracellular Iron in Switching Apoptosis to Ferroptosis to Target Therapy-Resistant Cancer Stem Cells
Santhi Latha Pandrangi,
Prasanthi Chittineedi,
Sphoorthi Shree Chalumuri,
Avtar Singh Meena,
Juan Alejandro Neira Mosquera,
Sungey Naynee Sánchez Llaguno,
Ramachandra Reddy Pamuru,
Gooty Jaffer Mohiddin,
Arifullah Mohammad
Affiliations
Santhi Latha Pandrangi
Onco-Stem Cell Research Laboratory, Department of Biochemistry and Bioinformatics, Institute of Science, GITAM Deemed to be University, Visakhapatnam 530045, India
Prasanthi Chittineedi
Onco-Stem Cell Research Laboratory, Department of Biochemistry and Bioinformatics, Institute of Science, GITAM Deemed to be University, Visakhapatnam 530045, India
Sphoorthi Shree Chalumuri
Onco-Stem Cell Research Laboratory, Department of Biochemistry and Bioinformatics, Institute of Science, GITAM Deemed to be University, Visakhapatnam 530045, India
Avtar Singh Meena
CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500007, India
Juan Alejandro Neira Mosquera
Department of Life Sciences and Agriculture, Armed Forces University-ESPE, Santo Domingo 230101, Ecuador
Sungey Naynee Sánchez Llaguno
Department of Life Sciences and Agriculture, Armed Forces University-ESPE, Santo Domingo 230101, Ecuador
Ramachandra Reddy Pamuru
Department of Biochemistry, Yogivemana University, Kadapa 516005, India
Gooty Jaffer Mohiddin
Department of Life Sciences and Agriculture, Armed Forces University-ESPE, Santo Domingo 230101, Ecuador
Arifullah Mohammad
Department of Agriculture Science, Faculty of Agro-Based Industry, Universiti Malaysia Kelantan, Jeli 17600, Malaysia
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.
