The natural compound n-butylidenephthalide suppresses type II ovarian cancer cell growth by inducing ferroptosis

Sep 23, 2026

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Type II high-grade serous ovarian cancer (HGSOC) is a major ovarian cancer subtype, and metastasis plus chemotherapy resistance are linked to cancer stem cells (CSCs). This study evaluates whether the natural compound n-butylidenephthalide (BP) affects ferroptosis to suppress HGSOC growth. CSCs were isolated using ALDH, and cell survival, proliferation, IC50, TUNEL, Western blot, and qPCR were applied. In vivo, xenograft models showed BP inhibits growth via ferroptosis through GPX4 conventional and HMBOX-1 noncanonical pathways, and combined BP with Taxol improved anti-tumor effects.

LanguageEnglish

CategoryHealthcare

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Pages14

Reading Time35 min

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Abstract

Introduction

Ivyspring International Publisher InternationalJournal of Medical Sciences 2025; 22(15): 3854-3867. doi: 10.7150/ijms.114086 Research Paper The natural compound n-butylidenephthalide suppresses type II ovarian cancer cell growth by inducing ferroptosis Shinn-Zong Lin1,2, Chih-Yang Huang3,4,5,6,7, Yueh-Min Lin8,9, Rathinasamy Baskaran3, Yu-Jung Lin3,10, Wei-Wen Kuo11,12,13, Dah-Ching Ding14,15􀀍 1. Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. 2. Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. 3. Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. 4. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. 5. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan. 6. Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan. 7. Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan. 8. Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan. 9. School of Medicine, Chung Shan Medical University, Taichung, Taiwan. 10. Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan. 11. Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan. 12. Ph.D. Program for Biotechnology Industry, China Medical University, Taichung, Taiwan. 13. School of Pharmacy, China Medical University, Taichung, Taiwan. 14. Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan. 15. Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan. 􀀍 Corresponding author: Dr. Dah-Ching Ding, MD, Ph.D., Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Foundation, Tzu Chi University, No. 707, Chung-Yang Rd., Sec. 3, Hualien, Taiwan, [R.O.C. Email: dah1003@yahoo.com.tw](R.O.C. Email: dah1003@yahoo.com.tw); Tel: +886-3-8561825-13383, Fax: +886-3-8577161.© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions. Received: 2025.03.20; Accepted: 2025.07.07; Published: 2025.08.22 Abstract Type II high-grade serous ovarian cancer (HGSOC) accounts for 80% of all ovarian cancers. Tumor metastasis and chemotherapy resistance are predominantly caused by cancer stem cells (CSCs). n-butylidenephthalide (BP) has showed promise as an anti-tumor drug in a variety of malignancies. The purpose of this study was to examine the ferroptosis influence of BP on HGSOC. CSCs were isolated from the HGSOC cell lines KURAMOCHI and OVSAHO by employing the CSC marker ALDH. The study assessed cell survival, proliferation, IC50 (the concentration at which 50% growth suppression occurs), terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) assay, and Western blot analysis of ovarian cancer cells and CSCs. qPCR was performed to assess ferroptosis-related gene expression. Furthermore, animal studies were carried out using a mouse model with subcutaneous xenografted stemness-enriched ovarian CSCs and evaluated with an IVIS scan. In this in vivo investigation, control, BP with or without taxol or ferrostatin were intended as cancer treatments. The findings indicated that BP inhibits HGSOC growth via ferroptosis mediated by the GPX4 conventional and HMBOX-1 noncanonical pathways. Furthermore, the anti-tumor effects of BP and Taxol were significantly improved when tumor-bearing mice were treated wi

FAQs

What is the main goal of the study on n-butylidenephthalide (BP)?

To examine how BP influences ferroptosis and whether this mechanism suppresses HGSOC cell growth.

How were cancer stem cells (CSCs) isolated for the experiments?

CSCs were isolated from HGSOC cell lines using the CSC marker ALDH.

What mechanism does the study propose for BP’s anti-tumor effect?

BP inhibits HGSOC growth via ferroptosis mediated by the GPX4 conventional pathway and the HMBOX-1 noncanonical pathway.

Sep 23, 2026

Uploaded by Franzy