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<p>The <i>Elephantopus mollis</i> H.B.K. contains various sesquiterpene lactones that have shown anti-proliferative and proapoptotic effects in various cancers, although the underlying mechanisms are partially understood. Inducing of excessive ER stress is a potential cancer therapeutic strategy. However, ER stress activator remain limited in current clinical applications. In this study, we identified that EM-12, an uncovered sesquiterpene lactone isolated from <i>Elephantopus mollis</i> H.B.K., as a BiP ATPase activity inhibitor through BiP ATPase activity assay in vitro. This molecule also exhibits significantly greater cytotoxicity in numerous ovarian cancer cell lines, including paclitaxel-resistance ovarian cancer cell line, compared to transformed ovarian epithelial cell lines. In addition, EM-12 exerts broad-spectrum cytotoxicity against various human cancer cell lines, including liver, nasopharyngeal, and breast cancer cell lines. Mechanically, EM-12 promotes ER stress and ER-stress-related apoptosis to against cancer cells through inhibiting BiP ATPase activity.</p>

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EM-12, a natural sesquiterpene lactone extracted from Elephantopus mollis, promotes cancer cell apoptosis by activating ER stress

  • 期刊论文

  • 发表日期：

    2025年3月18日

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  • Xiang Huang,
  • Junzhen Zhou,
  • Zhenhua Li,
  • Meijun Ye,
  • Changyan Hou,
  • Qing Zhang,
  • Yuanhong Chen,
  • Qiang Li,
  • Fengying Li,
  • Xiaofeng Zhu,
  • Jianwei Jiang

摘要

The Elephantopus mollis H.B.K. contains various sesquiterpene lactones that have shown anti-proliferative and proapoptotic effects in various cancers, although the underlying mechanisms are partially understood. Inducing of excessive ER stress is a potential cancer therapeutic strategy. However, ER stress activator remain limited in current clinical applications. In this study, we identified that EM-12, an uncovered sesquiterpene lactone isolated from Elephantopus mollis H.B.K., as a BiP ATPase activity inhibitor through BiP ATPase activity assay in vitro. This molecule also exhibits significantly greater cytotoxicity in numerous ovarian cancer cell lines, including paclitaxel-resistance ovarian cancer cell line, compared to transformed ovarian epithelial cell lines. In addition, EM-12 exerts broad-spectrum cytotoxicity against various human cancer cell lines, including liver, nasopharyngeal, and breast cancer cell lines. Mechanically, EM-12 promotes ER stress and ER-stress-related apoptosis to against cancer cells through inhibiting BiP ATPase activity.