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.
Bibliographical noteFunding Information:
Funding: This work was supported by the National Research Foundation of Korea grant funded by the Ministry of Science and ICT, South Korea (grant number: 2018R1C1B6009048).
This work was supported by the National Research Foundation of Korea grant funded by the Ministry of Science and ICT, South Korea (grant number: 2018R1C1B6009048). Acknowledgments: We would also like to thank the School of Life Sciences and Biotechnology for BK21 PLUS, Korea University for supporting the publication fee.
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
- Calcium influx
- ER–mitochondria axis
- Ovarian cancer