Eupatilin promotes cell death by calcium influx through ER-mitochondria axis with SERPINB11 inhibition in epithelial ovarian cancer

Jin Young Lee, Hyocheol Bae, Changwon Yang, Sunwoo Park, Byung Soo Youn, Han Soo Kim, Gwonhwa Song, Whasun Lim

Research output: Contribution to journalArticle

Abstract

Ovarian cancer is the leading cause of gynecological cancer-related mortality. The anticancer effect of eupatilin, a family of flavonoids, is known in many cancer types, but it is unclear what mechanism it plays in ovarian cancer. In this study, eupatilin promoted cell death of ovarian cancer cells by activating caspases, cell cycle arrest, reactive oxygen species (ROS) generation, calcium influx, disruption of the endoplasmic reticulum (ER)–mitochondria axis with SERPINB11 inhibition, and downregulation of phosphoinositide 3-kinase (PI3K) and mitogen activated protein kinase (MAPK) pathways. Additionally, eupatilin-reduced SERPINB11 expression enhanced the effect of conventional chemotherapeutic agents against ovarian cancer cell progression. Cotreatment with siSERPINB11 and eupatilin increased calcium-ion-dependent apoptotic activity in ovarian cancer cells. Although there were no significant toxic effects of eupatilin on embryos, eupatilin completely inhibited tumorigenesis in a zebrafish xenograft model. In addition, eupatilin suppressed angiogenesis in zebrafish transgenic models. Collectively, downregulating SERPINB11 with eupatilin against cancer progression may improve therapeutic activity.

Original languageEnglish
Article number1459
Pages (from-to)1-20
Number of pages20
JournalCancers
Volume12
Issue number6
DOIs
Publication statusPublished - 2020 Jun

Keywords

  • Calcium influx
  • ER–mitochondria axis
  • Eupatilin
  • Ovarian cancer
  • SERPINB11

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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