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Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells

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机构： [1]Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Chi, Kunming 650201, Peoples R China [2]Univ Chinese Acad Sci, Beijing 100049, Peoples R China [3]Kunming Med Univ, Affiliated Hosp 1, Dept Orthoped, Kunming 650032, Peoples R China [4]Chinese Acad Med Sci, Res Unit Chem Biol Nat Antivirus Prod, Beijing 100730, Peoples R China [5]Chinese Acad Sci, Yunnan Key Lab Nat Med Chem, Kunming Inst Bot, Kunming 650201, Peoples R China

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关键词： Ferroptosis Pacidusin B ER stress PERK-Nrf2-HO-1 pathway xCT

摘要：

Cancer cells generally exhibit 'iron addiction' phenotypes, which contribute to their vulnerability to ferroptosis inducers. Ferroptosis is a newly discovered form of programmed cell death caused by iron-dependent lipid peroxidation. In the present study, pacidusin B, a dichapetalin-type triterpenoid from Phyllanthus acidus (L.) Skeels (Euphorbiaceae), induces ferroptosis in the HT1080 human fibrosarcoma cell line. Cells treated with pacidusin B exhibited the morphological characteristic 'ballooning' phenotype of ferroptosis. The biochemical hallmarks of ferroptosis were also observed in pacidusin B-treated cells. Both oxidative stress and ER stress play significant roles in pacidusin B-induced ferroptosis. The activation of the PERK-Nrf2-HO-1 signaling pathway led to iron overload, while inhibition of GPX4 further sensitized cancer cells to ferroptosis. Furthermore, the molecular docking study showed that pacidusin B docked in the same pocket in xCT as the ferroptosis inducer erastin. These results revealed that pacidusin B exerts anticancer effects via inducing ER-mediated ferroptotic cell death.

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大类 | 3 区化学

小类 | 3 区药物化学

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Q1 CHEMISTRY, MEDICINAL

影响因子： 4.8 最新[2023版] 3.9 最新五年平均 0 出版当年[2024版] 0 出版当年五年平均 4.8 出版前一年[2023版]

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第一作者机构： [1]Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Chi, Kunming 650201, Peoples R China [2]Univ Chinese Acad Sci, Beijing 100049, Peoples R China

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通讯机构： [1]Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Chi, Kunming 650201, Peoples R China [4]Chinese Acad Med Sci, Res Unit Chem Biol Nat Antivirus Prod, Beijing 100730, Peoples R China [5]Chinese Acad Sci, Yunnan Key Lab Nat Med Chem, Kunming Inst Bot, Kunming 650201, Peoples R China

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