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α‐Mangostin promotes apoptosis of human rheumatoid arthritis fibroblast‐like synoviocytes by reactive oxygen species‐dependent activation of ERK1/2 mitogen‐activated protein kinase
Author(s) -
Sheng Xiaoyun,
Li Jun,
Zhang Chao,
Zhao Lianggong,
Guo Laiwei,
Xu Tianen,
Jin Jiaxin,
Wu Meng,
Xia Yayi
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28760
Subject(s) - reactive oxygen species , apoptosis , kinase , viability assay , protein kinase a , chemistry , microbiology and biotechnology , cytochrome c , phosphorylation , p38 mitogen activated protein kinases , fibroblast , signal transduction , pharmacology , cancer research , biology , biochemistry , in vitro
α‐Mangostin (α‐M) is a commonly used traditional medicine with various biological and pharmacological activities. Our study aimed to explore the effects and mechanism of α‐M in regulating apoptosis of rheumatoid arthritis fibroblast‐like synoviocytes (RA‐FLS). α‐M of 10 to 100 μM was used to treat RA‐FLS for 24 hours, followed by measuring cell viability and apoptosis. The involvement of reactive oxygen species (ROS) and mitogen‐activated protein kinases was detected. Treatment of α‐M promoted apoptosis and reduced viability of RA‐FLS in a dose‐dependent manner. The mitochondrial membrane potential in RA‐FLS was remarkably reduced by α‐M treatment, accompanied by the cytochrome c accumulation in the cytosol and increased activities of caspase‐3 and caspase‐9. Moreover, we found that α‐M treatment promoted ROS production and extracellular signal‐regulated kinase 1/2 (ERK1/2) phosphorylation. The proapoptotic activity of α‐M in RA‐FLS was markedly reversed by the co‐induction with the ERK1/2 inhibitor LY3214996 or ROS scavenger N ‐acetyl‐ l ‐cysteine. In conclusion, our studies found that α‐M had remarkable proapoptotic activities in RA‐FLS, which is regulated by the induction of ROS accumulation and ERK1/2 phosphorylation. α‐M may thus have potential therapeutic effects for rheumatoid arthritis.