Toxicity of superparamagnetic iron oxide nanoparticles on retinoblastoma mitochondria.

PURPOSE: Retinoblastoma (RB) is one of the most important cancers in children with a higher rate of prevalence in developing countries. Despite different approaches to the treatment of RB, it seems necessary to discover a new approach to its treatment. Today, mitochondria are recognised as an important target in the treatment of cancer. Superparamagnetic iron oxide nanoparticles (SPIONs) have been studied by researchers due to their important biological effects. METHODS: In this study, the effects of SPIONs on mitochondria isolated from Y79 retinoblastoma cells were investigated. RESULTS: The results showed that SPIONs were able to increase the reactive oxygen species (ROS) level and subsequently damage the mitochondrial membrane and release cytochrome c a as one of the important pro-apoptotic proteins of RB mitochondria. Furthermore, the results indicated a decrease in cell viability and an increase in caspase-3 activity in Y79 retinoblastoma cells. CONCLUSIONS: These events can lead to the killing of cancerous mitochondria. Our results suggest that SPIONs can cause mitochondrial dysfunction and death in RB mitochondria.

Cold Atmospheric Plasma Versus Cisplatin Against Oral Squamous Cell Carcinoma: A Mitochondrial Targeting Study.

Plasma therapy and the study of the effects of cold atmospheric plasma (CAP) on tissues and living cells have been considered by scientific researchers in recent years. CAP is used in the treatment of cancer, but its anti-cancer mechanism has not been fully studied. Therefore, we studied the toxicity effect of CAP by using argon as feed gas and the synergistic effects of CAP with cisplatin on tumor cells and mitochondria isolated from tumor legions of the rat model of oral squamous cell carcinoma (OSCC). For this reason, we determined the possible toxic alterations of CAP on mitochondrial upstream events and activation of caspase-3 as the key major downstream event of apoptosis. Also, the effects of cisplatin (10 µM) as a positive control and its synergistic effects with CAP (IC50 concentration) were investigated. The results showed that CAP reduced mitochondrial dysfunction by reduction in succinate dehydrogenase (SDH) activity. Also, CAP in concentrations of 1200, 2400, and 4800 a.u. has been able to increase the level of reactive oxygen species (ROS), mitochondrial swelling, damage to the mitochondrial membrane, cytochrome c release, and activation of the final mediator of apoptosis (caspase-3) only in the OSCC group. CAP at 4800 a.u concentration had similar effects to cisplatin (10 µM). Synergistic effects between CAP (2400 a.u) and cisplatin (10 µM) have also been reported. Based on all results CAP showed positive and promising results on mitochondrial upstream parameters leading to activation of caspase-3, the final mediator of apoptosis only on OSCC cells and mitochondria without any significant effect on normal cells and mitochondria.

The selective toxicity of superparamagnetic iron oxide nanoparticles (SPIONs) on oral squamous cell carcinoma (OSCC) by targeting their mitochondria.

In recent years, many researchers have made tremendous efforts into using nanotechnology in biomedical applications and science, such as magnetic resonance imaging, drug delivery, and in particular, oncological therapeutic via superparamagnetic iron oxide nanoparticles (SPIONs). Head and neck squamous cell carcinoma (HNSCC) and especially oral squamous cell carcinoma (OSCC) have been a serious and ongoing concern. There are many strong emphases on the importance of toxic mechanisms due to oxidative stress and specifically, the changed cellular response. Therefore, our study was designed to evaluate the effects of SPIONs on OSCC mitochondria because of the usefulness of the application of these nanoparticles in cancer treatment and diagnosis. An increased level of reactive oxygen species (ROS) is one of the substantial mechanisms found for SPIONs in this study, and initially originated from disruption of the electron transfer chain shown by a decrease in mitochondrial succinate dehydrogenase activity. Increased ROS formation subsequently followed a decline of mitochondrial membrane potential, the release of mitochondrial cytochrome complex, and mitochondrial swelling in the OSCC mitochondria compared with almost no effect in normal mitochondria. In addition, the SPIONs decreased cell viability and increased lipid peroxidation level and caspase-3 activity in OSCC cells. The results represented that the exposure to the SPIONs induced selective toxicity only on the OSCC but not normal mitochondria. Based on our findings, we finally concluded that the SPIONs may be considered as a potential therapeutic candidate for the treatment of OSCC.

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.