Abstract
Tumor growth is associated with oxidative stress, which causes lipid peroxidation. The most intensively studied product of lipid peroxidation is 4-hydroxy-2-nonenal (HNE), which is considered as a “second messenger of free radicals” that binds to proteins and acts as a growth-regulating signaling factor. The incidence of squamous cell carcinoma of the oropharynx is associated with smoking, alcohol and infection of human papilloma virus (HPV), with increasing incidence world-wide. The aim of this retrospective study involving 102 patients was to determine the immunohistochemical appearance of HNE-protein adducts as a potential biomarker of lipid peroxidation in squamous cell carcinoma of the oropharynx. The HNE-protein adducts were detected in almost all tumor samples and in the surrounding non-tumorous tissue, while we found that HNE is differentially distributed in squamous cell carcinomas in dependence of clinical stage and histological grading of these tumors. Namely, the level of HNE-immunopositivity was increased in comparison to the normal oropharyngeal epithelium in well- and in moderately-differentiated squamous cell carcinoma, while it was decreasing in poorly differentiated carcinomas and in advanced stages of cancer. However, more malignant and advanced cancer was associated with the increase of HNE in surrounding, normal tissue. This study confirmed the onset of lipid peroxidation, generating HNE-protein adducts that can be used as a valuable bioactive marker of carcinogenesis in squamous cell carcinoma of the oropharynx, as well as indicating involvement of HNE in pathophysiological changes of the non-malignant tissue in the vicinity of cancer.
Highlights
Oxidative stress (OS) is the process of excessive production of reactive oxygen species (ROS), notably of free radicals, playing a major role in the etiology of major human diseases, including cancer.It occurs when the anti-oxidative capacities of cells and tissues are in disbalance with ROS, which causesMolecules 2020, 25, 868; doi:10.3390/molecules25040868 www.mdpi.com/journal/moleculesMolecules 2020, 25, 868 oxidative damage of cells
The cytotoxic effects of reactive aldehydes resemble the toxicity of ROS, but because of their higher chemical stability, these aldehydes can spread from the site of origin and react with major biomolecules, among which proteins appear to be the major target, even at the distant site
The HNE was expressed in endothelium and vascular walls of almost all tumor vessels and it was increased with the grade of malignancy. These findings suggest that lipid peroxidation (LPO) is a common process in all glial tumors generating that an increase of HNE may be associated with malignancy and neovascularization [23]
Summary
Oxidative stress (OS) is the process of excessive production of reactive oxygen species (ROS), notably of free radicals, playing a major role in the etiology of major human diseases, including cancer.It occurs when the anti-oxidative capacities of cells and tissues are in disbalance with ROS, which causesMolecules 2020, 25, 868; doi:10.3390/molecules25040868 www.mdpi.com/journal/moleculesMolecules 2020, 25, 868 oxidative damage of cells. Oxidative stress (OS) is the process of excessive production of reactive oxygen species (ROS), notably of free radicals, playing a major role in the etiology of major human diseases, including cancer. It occurs when the anti-oxidative capacities of cells and tissues are in disbalance with ROS, which causes. Excessive production of ROS induces lipid peroxidation (LPO), especially of omega-6-polyunsaturated acids, which evolves as the autocatalytic process generates highly reactive aldehydes, notably 4-hydroxy-2-nonenal (HNE), malondialdehyde (MDA) and acrolein (Figure 1) [2,3]. The most intensively studied product of lipid peroxidation is HNE, which is considered to be “the second messenger of free radicals” that affects pathophysiology of cells in various ways. Because of high reactivity with biomolecules and its multiple biological effects, HNE is a popular LPO product in the field of molecular oncology
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