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Hydrogen peroxide-induced oxidative stress and its impact on innate immune responses in lung carcinoma A549 cells
- Source :
- Molecular and Cellular Biochemistry. 450:135-147
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- The immune responses, involved in recognition of cancer-specific antigens, are of particular interest as this may provide major leads towards developing new vaccines and antibody therapies against cancer. An effective treatment for cancer is still a challenge because there are many mechanisms through which the tumor cells can escape the host immune surveillance. Oxidative stress or respiratory burst which is host’s mechanism to kill the foreign particles is used as defense mechanism by the tumor cells. The tumor cells uses this oxidative stress to form neo-antigens which in turn makes them undetectable and can escape the host immune surveillance. The human lung carcinoma (A549) cells were treated using 100 µM H2O2 to induce oxidative stress, and the extent oxidative modifications were detected at the level of membrane and proteins in form of lipid peroxidation and protein carbonyls respectively. Nitric oxide and iNOS levels were estimated by Griess assay and immunostaining, respectively. The oxidized tumor proteins were visualized on one-dimensional SDS–PAGE. The H2O2-treated (15 min and 24 h post-treatment) A549 cells were co-cultured with THP-1 cells to subsequently visualize the phagocytic activity by Giemsa and CFSE staining to understand the role of neo (oxidized) tumor antigens in eliciting alteration in immune responses. A significant decline in the percent engulfed cells and decrease in the levels of reactive oxygen species was observed. Immunohistostaining for p47phox, which is an important indicator of the oxygen-dependent phagocytosis, showed a decrease in its levels when cells were treated for only 15 min with 100 µM H2O2, whereas at 24-h post-treatment there was no change in the p47phox levels. The study has established oxidative stress as a new pathogenic mechanism of carcinogenesis and will open new avenues for clinical intervention, adjunct therapies for cancer, and its control at the initial stage by targeting these neo-antigens.
- Subjects :
- 0301 basic medicine
Lung Neoplasms
THP-1 Cells
Clinical Biochemistry
medicine.disease_cause
03 medical and health sciences
0302 clinical medicine
Immune system
Antigen
medicine
Humans
Molecular Biology
A549 cell
Innate immune system
biology
Chemistry
Hydrogen Peroxide
Cell Biology
General Medicine
Immunity, Innate
Respiratory burst
Oxidative Stress
030104 developmental biology
A549 Cells
030220 oncology & carcinogenesis
Cancer research
biology.protein
Antibody
Carcinogenesis
Oxidative stress
Subjects
Details
- ISSN :
- 15734919 and 03008177
- Volume :
- 450
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biochemistry
- Accession number :
- edsair.doi.dedup.....c5f66ed05a6fdc7c11c315e901a5d8b0