Calcium-oxidative stress signaling axis and casein kinase 1α mediate eryptosis and hemolysis elicited by novel p53 agonist inauhzin

• DOI: 10.1080/1120009x.2021.1963616
• Publication Date: 2021-08-19T18:20:57Z
• Authors: Mohammad A. Alfhili; Essa Alsalmi; Abdullah Aljedai; Jawaher Alsughayyir; Manal Abudawood; Ahmed M. Basudan
• Keywords: 0301 basic medicine; Indoles; Eryptosis; Casein Kinase Ialpha; Hemolysis; 3. Good health; Oxidative Stress; 03 medical and health sciences; Phenothiazines; Humans; Calcium; Tumor Suppressor Protein p53; Reactive Oxygen Species

Inauhzin (INZ) is a novel p53 agonist with antitumor activity. Anemia common side effect of chemotherapy and may arise from red blood cell (RBC) hemolysis or eryptosis. In this study, we investigate the mechanisms INZ toxicity in human RBCs. RBCs were isolated healthy donors treated concentrations (5-500 μM) for 24 h at 37 °C. Hemoglobin was photometrically measured, cells stained Annexin-V-FITC phosphatidylserine (PS), Fluo4/AM calcium, 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) oxidative stress. caused significant dose-responsive, calcium-dependent starting 40 μM. Furthermore, significantly increased Annexin-positive Fluo4 DCF fluorescence. The cytotoxicity also mitigated presence D4476. possesses hemolytic eryptotic potential characterized by membrane scrambling, intracellular calcium overload, shrinkage, stress secondary to influx extracellular space.