Surfactin induces ER stress-mediated apoptosis via IRE1-ASK1-JNK signaling in human osteosarcoma

Guo Shou Wang, Ji Ying Chen, Wei Cheng Chen, I. Chin Wei, Szu Wei Lin, Kuang Wen Liao, Tzu Sen Yang, Ju Fang Liu

研究成果: 雜誌貢獻文章同行評審

摘要

Osteosarcoma, one of primary bone tumor in children and young adults, has poor prognosis and drug resistances to chemotherapy. In order to reinforce the conventional therapies and antagonize the osteosarcoma in patients, a novel strategy is required for developing a new treatment. In this study, surfactin, a natural product from Bacillus subtilis, showed the efficiency of cell death in osteosarcoma, but not in normal cells. Surfactin triggers ER stress mechanism by promoting the aberrant Ca2+ release from ER lumen and ER-signaling to mitochondrial dysfunction following caspases activation mediating cell apoptosis. Surfactin-induced ER stress not only upregulated of glucose-regulated protein 78/94 and IRE1-ASK1-JNK pathway but also leading to calpains and Bcl-2 proteins family involving the release of cytochrome c. The releases into cytosol trigger the cleavage of caspase-9 and caspase-3 to induce cell apoptosis. In this study, surfactin demonstrated the potential functions to trigger the ER stress, ER stress-associated IRE1-ASK1-JNK signaling pathway, mitochondrial dysfunction, and caspase activations leading to programmed cell apoptosis. Importantly, implicating the signaling pathway that regulates the connection between ER stress and mitochondrial dysfunction causing apoptosis associated with surfactin. These results indicated a potential application of surfactin strengthen current conventional therapies.
原文英語
期刊Environmental Toxicology
DOIs
出版狀態已發佈 - 3月 2022

ASJC Scopus subject areas

  • 毒理學
  • 管理、監督、政策法律
  • 健康、毒理學和誘變

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