Molecular and Cellular Effects of Hydrogen Peroxide on Human Lung Cancer Cells: Potential Therapeutic Implications

Figure 1

Effects of H₂O₂ that may lead to cell death. H₂O₂ affects several compartments and proteins potentially leading to cell death. Oxidation of DNA bases enriched with guanine adducts like oxo8dG base ring fragmentation, sugar modification, covalent cross linking of DNA and protein, and induction of DNA strand breaks may occur as a result of oxidative DNA damage induced by H₂O₂ [22]. Chk2 plays a major role in arresting the cell cycle progression in response to DNA damage [23]. Phosphorylation of Cdc25C and Cdc25A by Chk2 prevents cell cycle progression [24]. DDR involves the activation of the kinases ATM and Chk2 and their downstream effector p53 and its target axis [25, 26]. Overexpression of Aco-2 reduced oxidant-induced mtDNA lesions, mitochondrial p53 translocation, and apoptosis. Bcl-2 family proteins control the relocalization and actions of cytochrome C, a relevant step of apoptotic cell death [27]. H₂O₂ also increases caspase-3/caspase-7 activity [28] and upregulates the cleaved-caspase-9 [27], modifying the ΔΨm [28]. Apoptosis is also related with increased Ca²⁺ concentration that may be increased by influx via TRP ion channels or released from intracellular stores [29–31].