Agrimonolide inhibits cancer progression and induces ferroptosis and apoptosis by targeting SCD1 in ovarian cancer cells

Ying Liu; Xiaobei Liu; Hui Wang; Pingping Ding; Changlin Wang

doi:10.1016/j.phymed.2022.154102

Agrimonolide inhibits cancer progression and induces ferroptosis and apoptosis by targeting SCD1 in ovarian cancer cells

Phytomedicine. 2022 Jul:101:154102. doi: 10.1016/j.phymed.2022.154102. Epub 2022 Apr 21.

Authors

Ying Liu¹, Xiaobei Liu², Hui Wang³, Pingping Ding⁴, Changlin Wang⁵

Affiliations

¹ Department of Obstetrics and Gynecology, Yantai Zhifu Hospital, Yantai, Shandong, 266000, P.R. China.
² Department of Reproductive Genetics, Taian City Central Hospital, Taian, Shandong, 271000, P.R. China.
³ Department of Obstetrics, Taian City Central Hospital, Taian, Shandong, 271000, P.R. China.
⁴ Department of Gynecology, Affiliated Hospital of Shandong University of traditional Chinese Medicine, Jinan, Shandong, 250011, P.R. China.
⁵ Department of Gynecology, Taian City Central Hospital, Taian, Shandong, 271000, P.R. China. Electronic address: wchlfk@tom.com.

PMID: 35526323
DOI: 10.1016/j.phymed.2022.154102

Abstract

Background: Ovarian cancer is a gynaecological tumour has high incidence and mortality rates. Agrimonolide, isolated from Agrimonia pilosa Ledeb, has multiple biomedical activities, including anticancer activity.

Purpose: Here, we aimed to reveal the function of agrimonolide on ovarian cancer progression.

Methods: MTT assay, colony-formation assay, flow cytometry, transwell assay, scratch test, western immunoblotting, reactive oxygen species (ROS) detection, and ferroptosis analysis were performed to reveal the role and underlying mechanisms of agrimonolide in ovarian cancer cell lines (A2780 and SKOV-3). The effects of agrimonolide on the SKOV-3 xenograft model were also studied.

Results: Agrimonolide dose-dependently inhibited proliferation, migration, and invasion and promoted apoptosis in A2780 and SKOV-3 cells. Agrimonolide induced ferroptosis in tumour cells, evidenced by the increased levels of ROS, total iron, and Fe²⁺ and downregulation of ferroptosis indicators (SLC7A11 and GPX4). The SwissTargetPrediction and Comparative Toxicogenomics Database predicted SCD1 as a target protein for agrimonolide. Molecular Operating Environment software docked agrimonolide in the SCD1 protein, and the binding energy of interaction was -8.21 kcal/mol. The effects of agrimonolide on proliferation, invasion, and induction of apoptosis and ferroptosis were attenuated by SCD1 overexpression in A2780 and SKOV-3 cells. Additionally, agrimonolide attenuated the tumour growth of ovarian cancer in the SKOV-3 xenograft model and significantly downregulated SCD1 in tumour tissues.

Conclusion: Our study is the first to suggest that agrimonolide acts as a novel apoptosis- and ferroptosis-inducing agent in ovarian cancer cells by targeting SCD1. Agrimonolide may be a novel therapeutic agent for treating ovarian cancer.

Keywords: Agrimonolide; Ferroptosis; Ovarian cancer; SCD1.

MeSH terms

Apoptosis
Cell Line, Tumor
Cell Proliferation
Female
Ferroptosis*
Humans
Isocoumarins
Ovarian Neoplasms* / drug therapy
Ovarian Neoplasms* / pathology
Reactive Oxygen Species
Stearoyl-CoA Desaturase

Substances

Isocoumarins
Reactive Oxygen Species
agrimonolide
SCD1 protein, human
Stearoyl-CoA Desaturase