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.
Department of Bio and Nanochemistry, Kookmin University, Seoul, Korea.
Joon Ki
JK
Kim
School of Medicine, Jeju National University, Jeju, Korea.
Kyoung Ah
KA
Kang
School of Medicine, Jeju National University, Jeju, Republic of Korea.
Mei Jing
MJ
Piao
School of Medicine, Jeju National University, Jeju, Korea.
Madduma Hewage Susara Ruwan
MH
Kumara
Department of Bio and Nanochemistry, Kookmin University, Seoul, Korea.
Yong Joo
YJ
Jeong
Jeju Biodiversity Research Institute, Jeju Technopark, Jeju, Republic of Korea.
Mi Hee
MH
Ko
School of Medicine, Jeju National University, Jeju, Republic of Korea.
Jin Won
JW
Hyun
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D000459:Phaeophyceae / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species