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

doi:10.3390/cancers12061459

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

Department of Science Education

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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 language	English
Article number	1459
Pages (from-to)	1-20
Number of pages	20
Journal	Cancers
Volume	12
Issue number	6
DOIs	https://doi.org/10.3390/cancers12061459
State	Published - Jun 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Calcium influx
ER–mitochondria axis
Eupatilin
Ovarian cancer
SERPINB11

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/cancers12061459

Cite this

@article{ead2080182a14b2d9a4f415033577fa3,

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

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.",

keywords = "Calcium influx, ER–mitochondria axis, Eupatilin, Ovarian cancer, SERPINB11",

author = "Lee, {Jin Young} and Hyocheol Bae and Changwon Yang and Sunwoo Park and Youn, {Byung Soo} and Kim, {Han Soo} and Gwonhwa Song and Whasun Lim",

note = "Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2020",

month = jun,

doi = "10.3390/cancers12061459",

language = "English",

volume = "12",

pages = "1--20",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "6",

}

TY - JOUR

T1 - Eupatilin promotes cell death by calcium influx through ER-mitochondria axis with SERPINB11 inhibition in epithelial ovarian cancer

AU - Lee, Jin Young

AU - Bae, Hyocheol

AU - Yang, Changwon

AU - Park, Sunwoo

AU - Youn, Byung Soo

AU - Kim, Han Soo

AU - Song, Gwonhwa

AU - Lim, Whasun

PY - 2020/6

Y1 - 2020/6

N2 - 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.

AB - 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.

KW - Calcium influx

KW - ER–mitochondria axis

KW - Eupatilin

KW - Ovarian cancer

KW - SERPINB11

UR - http://www.scopus.com/inward/record.url?scp=85086127749&partnerID=8YFLogxK

U2 - 10.3390/cancers12061459

DO - 10.3390/cancers12061459

M3 - Article

AN - SCOPUS:85086127749

SN - 2072-6694

VL - 12

SP - 1

EP - 20

JO - Cancers

JF - Cancers

IS - 6

M1 - 1459

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this