Mechanistic Perspectives on Cutaneous Toxicity Induced by the Multitargeted Kinase Inhibitor Sunitinib
Tuğçe Boran1, Gül Küçükkahraman2, Mahmoud Abudayyak31Department of Pharmaceutical Toxicology, Faculty of Pharmacy, İstanbul University-Cerrahpaşa, İstanbul, Türkiye, 2Institute of Health Sciences, Istanbul University, İstanbul, Türkiye, 3Department of Pharmaceutical Toxicology, Faculty of Pharmacy, İstanbul University, İstanbul, Türkiye
Objectives: Multittargeted kinase inhibitor sunitinib is used for the treatment of some cancer types. It has been noted that sunitinib can cause cutaneous reactions and their mechanisms have not been known yet. The study aimed to investigate mechanistic bases of sunitinib-induced cutaneous reactions using HaCaT cell line. Methods: Cytotoxicity of sunitinib was evaluated with MTT assay following 72 h exposure. Reactive oxygen species (ROS) generation and apoptotic/necrotic cell death were examined by flow cytometer, and mitochondrial membrane potential (MMP) was assessed by microplate reader with fluorescent dyes. Changes in malondialdehyde, reduced and oxidized glutathione levels were determined using ELISA kits. DNA damage was investigated with alkaline single gel electrophoresis (Comet) assay. Results: Half maximal inhibitory concentration of sunitinib was determined as 3.10 ?M after 72 h exposure. Our findings showed that sunitinib provokes ROS generation, glutathione and lipid oxidation especially at the highest concentration. MMP hyperpolarization was observed at high doses. Apoptosis was triggered at the highest dose, while necrosis and DNA damage were induced at all exposure groups upon sunitinib exposure. Conclusion: Oxidative stress, cell death and DNA damage could be underlying causes of sunitinib-induced cutaneous reactions. Nevertheless, further studies are needed to confirm our findings. Keywords: Sunitinib, Cutenous reactions, Oxidative stress, Cell death
Cite This Article
Boran T, Küçükkahraman G, Abudayyak M. Mechanistic Perspectives on Cutaneous Toxicity Induced by the Multitargeted Kinase Inhibitor Sunitinib. EJMI. 2026; 10(1): 11-17
Corresponding Author: Tuğçe Boran