2. Academic Validation
  3. Norcantharidin inhibits the METTL16/MAT2A pathway to induce apoptosis and suppress tumor progression in ovarian cancer

Norcantharidin inhibits the METTL16/MAT2A pathway to induce apoptosis and suppress tumor progression in ovarian cancer

  • Arch Biochem Biophys. 2025 Sep:771:110510. doi: 10.1016/j.abb.2025.110510.
Yuan-Yuan Zhang 1,  Qiu-Xia Zeng 1,  Li Wang 1,  Kong-Xian Li 1,  Shun Zhang 2,  Ping Wan 3,  Xue-Ming Zhou 4,  Qi Chen 5
Affiliations

Affiliations

  • 1 Department of Obstetrics & Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People's Republic of China.
  • 2 Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People's Republic of China.
  • 3 Department of Gynecology of Traditional Chinese Medicine, The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, 330006, Jiangxi Province, People's Republic of China.
  • 4 Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People's Republic of China.
  • 5 Department of Obstetrics & Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People's Republic of China. Electronic address: chenqicq991@126.com.
PMID: 40517800 DOI: 10.1016/j.abb.2025.110510
Abstract

Objective: This study aimed to investigate the antitumor effects of norcantharidin (NCTD) in ovarian Cancer and to elucidate its molecular targets and mechanisms of action, with a focus on the methyltransferase-like protein 16 (METTL16)/methionine adenosyl transferase II alpha (MAT2A) signaling axis.

Materials and methods: Expression levels of METTL16 and MAT2A were analyzed in ovarian Cancer tissues and cells using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting. Human ovarian Cancer cell lines (ES2 and SKOV3) were cultured and subjected to METTL16 overexpression via gene recombination. The cytotoxic effects of varying concentrations of NCTD were assessed using the Cell Counting Kit-8 assay. Apoptosis, proliferation, and migration were evaluated through flow cytometry and wound healing (scratch) assays. A subcutaneous xenograft model of human ovarian Cancer was established in nude mice to assess in vivo antitumor efficacy. Enzyme-linked immunosorbent assay was used to quantify intracellular levels of S-adenosylmethionine (SAM).

Results: METTL16 and MAT2A gene expression levels were significantly elevated in ovarian Cancer tissues and cell lines (p < 0.05). Treatment with NCTD at 10 μg/mL significantly inhibited proliferation and induced Apoptosis in ES2 and SKOV3 cells. NCTD also suppressed cellular migration and angiogenic activity, with downregulation of related gene expression, effects that were attenuated by METTL16 overexpression (p < 0.05). In the xenograft model, NCTD administration significantly reduced tumor volume and downregulated expression of METTL16, MAT2A, protein Phosphatase 2A (PP2A), and vascular endothelial growth factor (p < 0.05).

Conclusions: NCTD exerts antineoplastic effects in ovarian Cancer by reducing intracellular S-adenosylmethionine levels, promoting PP2A demethylation, and inhibiting the METTL16/MAT2A signaling pathway. These effects contribute to cell cycle arrest, suppressed proliferation, and enhanced Apoptosis, supporting the therapeutic potential of NCTD in ovarian malignancies.

Keywords

Methionine adenosyltransferase 2A; Methyltransferase-like protein 16; Norcantharidin; Ovarian cancer; S-adenosylmethionine.

Figures
Products