Selenium‑induced redox imbalance triggers oxidative DNA damage and the p53‑dependent apoptosis of CHL‑1 human melanoma cells

Abstract

Melanoma, an aggressive type of cancer, is known for its ability to adapt to redox changes and resist standard treatments.Targeting the inherent redox weaknesses of melanoma has become a promising approach in research on redox-based cancer therapies.The present study investigated the toxic and DNA-damaging effects of elemental selenium (Se 0 ) on CHL-1 human melanoma cells and its effects on p53-related cell death pathways.Cell survival was assessed using an MTT assay.Oxidative DNA damage was measured with the alkaline comet assay, which involved calculating the olive tail moment (OTM) and the percentage of tail DNA (% tail DNA).In addition, the expression levels of the genes p53, p21, caspase-3 and Bcl-2 were measured using reverse transcription-quantitative PCR.Hydrogen peroxide (H 2 O 2 ) was used to induce oxidative stress, permitting the assessment of redox sensitization.Exposure to Se 0 reduced CHL-1 cell viability, which is based on both the concentration and duration of exposure; the IC 50 value was determined to be 7.50 M after 48 h.The results revealed that the combination of Se 0 and hydrogen peroxide produced more oxidative DNA damage than either treatment alone, due to increasing levels of oxidative stress, as indicated by significant increases in OTM and % tail DNA.Selenium-induced oxidative DNA damage was associated with the activation of p53, p21, and caspase-3, and the significantly downregulation of Bcl-2, combined with the activation of p53-mediated cell cycle arrest and intrinsic pathways for apoptosis.The findings of the present study suggest that selenium may promote redox imbalance and oxidative damage in CHL-1 melanoma cells by activating the p53-regulated apoptotic signaling pathway.Therefore, additional investigations are warranted in later-stage preclinical models to recognize the role of selenium as a redox-modulating agent that may increase the susceptibility of melanoma cells to oxidative stress.