Generation of Reactive Oxygen Species and Endoplasmic Reticulum Stress by Dictyopteris undulata Extract Leads to Apoptosis in Human Melanoma Cells.

In this study, we evaluated the hypothesis that a marine brown algae, Dictyopteris undulata ethanol extract (DUE), provokes apoptosis in a human melanoma cell line, A2058, via reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress. DUE inhibited A2058 cell proliferation and increased apoptotic body formation, as indicated by the presence of fragmented nuclei and the activation of caspase-3. Moreover, DUE-treated cells showed elevated ER staining, mitochondrial calcium cation (Ca2+) overloading, augmented levels of ER stress-related and cell death modulatory proteins, including RNA-dependent protein kinase-related ER kinase, phospho-inositol-requiring enzyme 1α, phospho-eukaryotic translation initiation factor 2α, and CCAAT/enhancer-binding protein-homologous protein, as well as increased intracellular ROS levels. However, the antioxidant N-acetyl cysteine reversed the elevated ROS levels, decreased apoptosis, and mitigated ER stress in A2058 cells following DUE treatment. These findings suggest that DUE treatment triggers apoptosis in human melanoma cells through a mechanism involving ER stress and ROS.