Abstract
Clear-cell renal carcinoma (ccRCC) is the most common type of renal cancer. The importance of oxidative stress in the context of this disease has been described, although there is only little information concerning the role of superoxide dismutase (SOD) enzymes. The importance of SOD in different pathological conditions promoted the development of SOD mimics (SODm). As such, manganese(III) porphyrins can mimic the natural SOD enzymes and scavenge different reactive oxygen species (ROS), thus modulating the cellular redox status. In this study, the exposure of 786-O human renal cancer cells to MnTnHex-2-PyP5+ (MnP), a very promising SODm, led to a concentration and time-dependent decrease in cell viability and in the cell proliferation indices, as well as to an increase in apoptosis. No relevant effects in terms of micronuclei formation were observed. Moreover, the exposure to MnP resulted in a concentration-dependent increase in intracellular ROS, presumably due to the generation of H2O2 by the inherent redox mechanisms of MnP, along with the limited ability of cancer cells to detoxify this species. Although the MnP treatment did not result in a reduction in the collective cell migration, a significant decrease in chemotactic migration was observed. Overall, these results suggest that MnP has a beneficial impact on reducing renal cancer cell viability and migration and warrant further studies regarding SODm-based therapeutic strategies against human renal cancer.
Highlights
Renal cell carcinoma (RCC) comprises up to 5% of all malignant tumors [1,2,3]
The effect of Manganese(III) porphyrins (MnPs) treatment on cell viability was assessed through different methodologies
The viability of MnP-exposed 786-O cells in medium containing 10% Fetal bovine serum (FBS) was assessed by Crystal Violet (CV) assay at 24 and 48 h periods (Figure 2)
Summary
Renal cell carcinoma (RCC) comprises up to 5% of all malignant tumors [1,2,3]. A substantial amount of new information concerning the epidemiology, molecular and immunologic characteristics of RCC as well as novel therapies has emerged. Several studies suggested a genetic basis for renal cell carcinoma [4,5]. Clear-cell renal carcinoma (ccRCC) is the most common type of renal cancer, accounting for approximately 75% of renal epithelial malignancies [5,6]. The main feature of ccRCC includes a hypoxia status with the activation of angiogenesis. The majority of sporadic ccRCC is associated with defects in von Hippel–Lindau (VHL) tumor suppressor gene [6,7]. The Antioxidants 2019, 8, 490; doi:10.3390/antiox8100490 www.mdpi.com/journal/antioxidants
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