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

doi:10.1007/s13659-024-00454-y

应用天然产物 ›› 2024, Vol. 14 ›› Issue (5): 34-34.DOI: 10.1007/s13659-024-00454-y

• ORIGINAL ARTICLES • 下一篇

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

Guangyu Zhu^1,2, Dian Luo^1,2, Yueqin Zhao^1,2, Zhengrui Xiang^1,2, Chao Chen^1,3, Na Li¹, Xiaojiang Hao^1,4, Xiao Ding^1,4, Yingjun Zhang^1,5, Yuhan Zhao¹

1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China;
2. University of Chinese Academy of Sciences, Beijing, 100049, China;
3. Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China;
4. Research Unit of Chemical Biology of Natural Anti-Virus Products, Chinese Academy of Medical Sciences, Beijing, 100730, China;
5. Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China

收稿日期:2024-02-12 出版日期:2024-10-24 发布日期:2024-10-14
通讯作者: Xiao Ding,E-mail:dingxiao@mail.kib.ac.cn;Yingjun Zhang,E-mail:zhangyj@mail.kib.ac.cn;Yuhan Zhao,E-mail:zhaoyuhan@mail.kib.ac.cn
基金资助:
This research was supported financially by grants from the CAS “Light of West China” Program, National Natural Science Foundation of China (82073740, 82293683 (82293680), 32270426, and 32000548), CAMS Innovation Fund for Medical Sciences (CIFMS, 2021-I2M-5-004), Natural Science Foundation of Yunnan Province (202301AT070282), Yunnan Revitalization Talent Support Program “Young Talent” Project (YNQR-QNRC-2019-091), the CAS Pioneer Hundred Talents Program, talent program from Kunming Institute of Botany CAS, and grant from Yunnan Province Science and Technology Department (202305AH340005).

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

Guangyu Zhu^1,2, Dian Luo^1,2, Yueqin Zhao^1,2, Zhengrui Xiang^1,2, Chao Chen^1,3, Na Li¹, Xiaojiang Hao^1,4, Xiao Ding^1,4, Yingjun Zhang^1,5, Yuhan Zhao¹

1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China;
2. University of Chinese Academy of Sciences, Beijing, 100049, China;
3. Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China;
4. Research Unit of Chemical Biology of Natural Anti-Virus Products, Chinese Academy of Medical Sciences, Beijing, 100730, China;
5. Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China

Received:2024-02-12 Online:2024-10-24 Published:2024-10-14
Contact: Xiao Ding,E-mail:dingxiao@mail.kib.ac.cn;Yingjun Zhang,E-mail:zhangyj@mail.kib.ac.cn;Yuhan Zhao,E-mail:zhaoyuhan@mail.kib.ac.cn
Supported by:
This research was supported financially by grants from the CAS “Light of West China” Program, National Natural Science Foundation of China (82073740, 82293683 (82293680), 32270426, and 32000548), CAMS Innovation Fund for Medical Sciences (CIFMS, 2021-I2M-5-004), Natural Science Foundation of Yunnan Province (202301AT070282), Yunnan Revitalization Talent Support Program “Young Talent” Project (YNQR-QNRC-2019-091), the CAS Pioneer Hundred Talents Program, talent program from Kunming Institute of Botany CAS, and grant from Yunnan Province Science and Technology Department (202305AH340005).

摘要/Abstract

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.

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

Abstract: 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.

Key words: Ferroptosis, Pacidusin B, ER stress, PERK-Nrf2-HO-1 pathway, xCT

Guangyu Zhu, Dian Luo, Yueqin Zhao, Zhengrui Xiang, Chao Chen, Na Li, Xiaojiang Hao, Xiao Ding, Yingjun Zhang, Yuhan Zhao. Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells[J]. 应用天然产物, 2024, 14(5): 34-34.

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

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

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