2. Academic Validation
  3. Scutellarin triggers ferroptosis in ovarian cancer cells via inhibiting AKT/mTOR and JAK2/STAT3 pathways

Scutellarin triggers ferroptosis in ovarian cancer cells via inhibiting AKT/mTOR and JAK2/STAT3 pathways

  • Med Oncol. 2025 Nov 25;43(1):24. doi: 10.1007/s12032-025-03144-y.
Siyi Wang # 1,  Minjing Zhang # 2 3,  Chao Tang 2 3,  Tian Xia 2 3,  Li Gao 4,  Qin Chen 5,  Feng Gao 6,  Weifeng Ye 2,  Huijuan Wang 2,  Meiyi Jin 7,  Xi Jiang 7,  Lijuan Gao 7,  Zheming Xu 2 3,  Runzhi Zhu 2 3,  Xiang Yan 2 3,  Jingyu Zhu 6,  Zhimin Ye 8,  Jieping Yan 9,  Gensheng Zhang 10 11,  Wenwen Wang 12
Affiliations

Affiliations

  • 1 Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China.
  • 2 Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310052, China.
  • 3 Zhejiang Key Laboratory of Neonatal Diseases, Hangzhou 310052, China.
  • 4 Center for Clinical Pharmacy, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China.
  • 5 Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China.
  • 6 Department of Urology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou 310007, China.
  • 7 School of Pharmacy, Hangzhou Medical College, Hangzhou 310059, China.
  • 8 Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China.
  • 9 Center for Clinical Pharmacy, Department of Pharmacy, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China. [email protected].
  • 10 Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310052, China. [email protected].
  • 11 Zhejiang Key Laboratory of Neonatal Diseases, Hangzhou 310052, China. [email protected].
  • 12 Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China. [email protected].
  • # Contributed equally.
PMID: 41288840 DOI: 10.1007/s12032-025-03144-y
Abstract

Ovarian Cancer (OC) ranks as the second most prevalent gynecologic malignancy worldwide, largely attributed to the difficulties in detecting early stages, frequent disease reappearance, and unresponsiveness to existing therapies. Contemporary treatment selections for individuals with OC remain limited. Scutellarin (Scu), an active compound, demonstrates suppressive properties against multiplication, invasion, and survival of certain Cancer cell types. Nevertheless, the exact anti-cancer properties and molecular pathways of Scu in OC are still not fully understood. This investigation sought to examine the therapeutic impact of Scu and its potential mechanisms in OC. A series of assays, encompassing cell counting kit-8 (CCK-8), colony-formation assay, EdU staining, scratch/wound healing assay, matrigel invasion assay, DHE staining, flow cytometry, Western blotting, ferrous ion content assay kit, and immunofluorescence staining were employed to investigate the role and mechanisms of Scu in OC cell lines (SKOV3 and HO-8910). Scu markedly diminished cell viability, proliferation, and colony formation in both SKOV3 and HO-8910 cells. Scu substantially inhibited OC cells' migration, invasion, and epithelial-mesenchymal transition (EMT). Additionally, the flow cytometry data and Western blot results of Bax and Bcl-2 protein levels indicated that Scu induced cell Apoptosis in both SKOV3 and HO-8910 cells. Furthermore, Scu induced cell Ferroptosis by upregulating the levels of Reactive Oxygen Species (ROS), 4-hydroxynonenal (4-HNE), and Fe2+ while downregulating the expression of specificity protein 1 (SP1), solute carrier family 7 member 11 (SLC7A11), and Glutathione Peroxidase 4 (GPX4). The anti-cancer capabilities of Scu were also linked to the inhibition of the phosphorylated forms of Akt, mTOR, JAK2, and STAT3. Lastly, cell Apoptosis and Ferroptosis induced by Scu were counteracted by Akt Agonist SC79. The findings demonstrate that Scu effectively inhibited cell multiplication, migration, invasion, and EMT, while inducing oxidative stress, Apoptosis, and Ferroptosis in SKOV3 and HO-8910 cells. These effects were likely mediated by inhibiting the Akt/mTOR and JAK2/STAT3 signaling cascades. This investigation suggests that Scu holds potential as a promising chemotherapeutic agent for treating OC.

Keywords

AKT/mTOR; Ferroptosis; JAK2/STAT3; Ovarian cancer; Scutellarin.

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