Role of Mitochondria and Lysosomes in the Selective Cytotoxicity of Cold Atmospheric Plasma on Retinoblastoma Cells

Retinoblastoma (RB) is a common malignancy in childhood, with an incidence of 1 per 20,000 live births. Several approaches such as chemotherapy, laser, and radiotherapy have been used for the treatment of RB. However, the effectiveness of these methods is not sufficient and the mechanisms involved in the pathogenesis of the disease are not well understood. The disruption of the apoptotic process is considered as one of the mechanisms involved in the pathogenesis of RB. This study was designed to examine the in-vitro selective toxicity of cold atmospheric plasma (CAP) on RB cells’ mitochondria and lysosomes. The results showed that CAP decreased cell viability and GSH content and also increased caspase-3 activity and lipid peroxidation (LPO) in cancerous ocular cells isolated from the rat model of RB compared to the normal rat ocular cells. Furthermore, results demonstrated that CAP significantly increased ROS generation, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release only in cancerous rat ocular mitochondria but not the normal rat ocular mitochondria. Furthermore, our results demonstrated that CAP significantly increased the lysosomal damage only in the cancer group. Altogether, the results of the study showed that CAP could selectively induce apoptosis on RB mitochondria. CAP may therefore be considered as a promising candidate for further in-vivo and clinical researches to reach a new anti- RB drug.