Repositioning of cis-flupentixol for the suppression of ovarian cancer cell migration and invasion through ERK5 inhibition
4 affiliations
- 1Department of Biopharmaceutical Chemistry, Kookmin University, Seoul, 02707 Republic of Korea
- 2Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, 02707 Republic of Korea
- 3Antibody Research Institute, Kookmin University, Seoul, 02707 Republic of Korea
- 4Department of Medicine, University of Ulsan College of Medicine, Seoul, 05505 Republic of Korea
Abstract
Background: Ovarian cancer (OC) remains the most lethal gynecological malignancy, largely because of its late-stage diagnosis and limited effective screening modalities. Despite therapeutic advances, high relapse rates and therapeutic resistance—particularly in metastatic disease—underscore the urgent need for novel therapeutic strategies targeting OC cell dissemination. In this study, the effects of cis-flupentixol (cis-FP), a typical antipsychotic agent, on OC cell migration and invasion were investigated.
Methods: The effects of cis-FP on OC cell migration and invasion were evaluated using SKOV3 and OVCAR8 cells. Kinase profiling was performed to identify molecular targets of cis-FP, and mechanistic analyses were subsequently conducted to investigate the signaling pathways potentially associated with its inhibitory effects on OC cell motility.
Results: Our results showed that cis-FP significantly inhibited the migration and invasion of SKOV3 and OVCAR8 OC cells in a dose-dependent manner. Kinase profiling identified extracellular signal-regulated kinase 5 (ERK5) as a direct molecular target of cis-FP. Subsequent mechanistic analyses revealed that cis-FP reduced ERK5 autophosphorylation and altered focal adhesion kinase (FAK) phosphorylation, changes that were associated with impaired OC cell motility.
Conclusions: These findings demonstrate that cis-FP suppresses OC cell migration and invasion and identify ERK5 as a molecular target of cis-FP. Our results suggest that modulation of ERK5-associated signaling pathways may contribute to the inhibitory effects of cis-FP on OC cell motility.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s10020-026-01592-4.
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BibTeX
@article{kim2026repositioning,
title = {{Repositioning of cis-flupentixol for the suppression of ovarian cancer cell migration and invasion through ERK5 inhibition}},
author = {Li Hyun Kim and Yul Min Lee and Dain Kim and Hyun Jung Kim and Kyun Heo},
journal = {Molecular Medicine},
year = {2026},
month = aug,
doi = {10.1186/s10020-026-01592-4},
url = {https://doi.org/10.1186/s10020-026-01592-4},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Repositioning of cis-flupentixol for the suppression of ovarian cancer cell migration and invasion through ERK5 inhibition
AU - Li Hyun Kim
AU - Yul Min Lee
AU - Dain Kim
AU - Hyun Jung Kim
AU - Kyun Heo
PY - 2026
DA - 2026/08/07
JO - Molecular Medicine
DO - 10.1186/s10020-026-01592-4
UR - https://doi.org/10.1186/s10020-026-01592-4
AB - Background: Ovarian cancer (OC) remains the most lethal gynecological malignancy, largely because of its late-stage diagnosis and limited effective screening modalities. Despite therapeutic advances, high relapse rates and therapeutic resistance—particularly in metastatic disease—underscore the urgent need for novel therapeutic strategies targeting OC cell dissemination. In this study, the effects of cis-flupentixol (cis-FP), a typical antipsychotic agent, on OC cell migration and invasion were investigated. Methods: The effects of cis-FP on OC cell migration and invasion were evaluated using SKOV3 and OVCAR8 cells. Kinase profiling was performed to identify molecular targets of cis-FP, and mechanistic analyses were subsequently conducted to investigate the signaling pathways potentially associated with its inhibitory effects on OC cell motility. Results: Our results showed that cis-FP significantly inhibited the migration and invasion of SKOV3 and OVCAR8 OC cells in a dose-dependent manner. Kinase profiling identified extracellular signal-regulated kinase 5 (ERK5) as a direct molecular target of cis-FP. Subsequent mechanistic analyses revealed that cis-FP reduced ERK5 autophosphorylation and altered focal adhesion kinase (FAK) phosphorylation, changes that were associated with impaired OC cell motility. Conclusions: These findings demonstrate that cis-FP suppresses OC cell migration and invasion and identify ERK5 as a molecular target of cis-FP. Our results suggest that modulation of ERK5-associated signaling pathways may contribute to the inhibitory effects of cis-FP on OC cell motility. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s10020-026-01592-4.
SN - 1076-1551
SN - 1528-3658
ER -