5-Methoxyflavone suppresses nasopharyngeal carcinoma proliferation through regulating p53/SREBP/SCD signaling-mediated lipid synthesis and ferroptosis
- 1Department of Pathophysiology, School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, 524023 China
- 2The People’s Hospital of Gaozhou, Gaozhou, Guangdong, 525200 China
- 3Department of Head and Neck Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524023 China
Abstract
Background: Nasopharyngeal carcinoma (NPC) is a highly prevalent malignant epithelial tumor in southern China. Although early-stage NPC patients have a favorable prognosis with concurrent chemoradiotherapy, the limited efficacy of current clinical regimens remains a crucial obstacle in the treatment of advanced NPC patients. 5-Methoxyflavone, a methylated flavonoid, has been reported to exhibit diverse roles in anti-cancer activity and lipid modulation. However, its potential role in NPC remains unclear. This study aims to investigate the effect of 5-Methoxyflavone on NPC proliferation and its underlying mechanism.
Methods: MTT, colony formation, EdU assays, and flow cytometry were performed with various concentrations of 5-Methoxyflavone (0, 40, 60, 80 and 100 µM) to investigate its effect on NPC cell proliferation. A HONE1 xenograft model was established for in vivo validation. Immunoprecipitation and dual-luciferase reporter assay were employed to confirm 5-Methoxyflavone’s regulatory function on the p53/SREBPs pathway. Lipid synthesis was determined by measuring total cholesterol and triglycerides using ELISA and visualizing lipid droplets via Oil Red O staining. Ferroptosis was evaluated by detecting intracellular ferrous ions, lipid ROS, and glutathione (GSH) levels.
Results: 5-Methoxyflavone suppressed NPC cell proliferation in a concentration-dependent manner in vitro. In addition, it profoundly inhibited tumor xenograft growth in mice without causing obvious adverse toxicity. Mechanistically, 5-Methoxyflavone deubiquitinated and stabilized p53 via inhibiting MDM2 expression, leading to suppression of SREBPs and their downstream lipid synthesis-related genes, thus inhibiting lipid synthesis in NPC cells. p53 depletion counteracted 5-Methoxyflavone’s inhibitory effect, while SREBP1 knockdown restored proliferation in p53-silenced cells. Furthermore, 5-Methoxyflavone-stimulated downregulation of SREBP1/SCD signaling triggered ferroptosis in NPC cells by promoting iron accumulation, lipid peroxidation, and GSH depletion. Overexpression of SCD reversed the ferroptosis-inducing effects of 5-Methoxyflavone.
Conclusions: Our findings reveal that 5-Methoxyflavone inhibits NPC proliferation by blocking lipid synthesis and inducing ferroptosis via the p53/SREBPs/SCD signaling pathway, providing evidence for the development of innovative drugs for NPC treatment.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12896-026-01163-9.
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BibTeX
@article{cui20265methoxyflavone,
title = {{5-Methoxyflavone suppresses nasopharyngeal carcinoma proliferation through regulating p53/SREBP/SCD signaling-mediated lipid synthesis and ferroptosis}},
author = {Yiwen Cui and Yan Zhao and Rong Li and Mingyong Li and Tongyuan Deng and Bo Bao and Yingying Hu},
journal = {BMC Biotechnology},
year = {2026},
month = may,
doi = {10.1186/s12896-026-01163-9},
url = {https://doi.org/10.1186/s12896-026-01163-9},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 5-Methoxyflavone suppresses nasopharyngeal carcinoma proliferation through regulating p53/SREBP/SCD signaling-mediated lipid synthesis and ferroptosis
AU - Yiwen Cui
AU - Yan Zhao
AU - Rong Li
AU - Mingyong Li
AU - Tongyuan Deng
AU - Bo Bao
AU - Yingying Hu
PY - 2026
DA - 2026/05/18
JO - BMC Biotechnology
DO - 10.1186/s12896-026-01163-9
UR - https://doi.org/10.1186/s12896-026-01163-9
AB - Background: Nasopharyngeal carcinoma (NPC) is a highly prevalent malignant epithelial tumor in southern China. Although early-stage NPC patients have a favorable prognosis with concurrent chemoradiotherapy, the limited efficacy of current clinical regimens remains a crucial obstacle in the treatment of advanced NPC patients. 5-Methoxyflavone, a methylated flavonoid, has been reported to exhibit diverse roles in anti-cancer activity and lipid modulation. However, its potential role in NPC remains unclear. This study aims to investigate the effect of 5-Methoxyflavone on NPC proliferation and its underlying mechanism. Methods: MTT, colony formation, EdU assays, and flow cytometry were performed with various concentrations of 5-Methoxyflavone (0, 40, 60, 80 and 100 µM) to investigate its effect on NPC cell proliferation. A HONE1 xenograft model was established for in vivo validation. Immunoprecipitation and dual-luciferase reporter assay were employed to confirm 5-Methoxyflavone’s regulatory function on the p53/SREBPs pathway. Lipid synthesis was determined by measuring total cholesterol and triglycerides using ELISA and visualizing lipid droplets via Oil Red O staining. Ferroptosis was evaluated by detecting intracellular ferrous ions, lipid ROS, and glutathione (GSH) levels. Results: 5-Methoxyflavone suppressed NPC cell proliferation in a concentration-dependent manner in vitro. In addition, it profoundly inhibited tumor xenograft growth in mice without causing obvious adverse toxicity. Mechanistically, 5-Methoxyflavone deubiquitinated and stabilized p53 via inhibiting MDM2 expression, leading to suppression of SREBPs and their downstream lipid synthesis-related genes, thus inhibiting lipid synthesis in NPC cells. p53 depletion counteracted 5-Methoxyflavone’s inhibitory effect, while SREBP1 knockdown restored proliferation in p53-silenced cells. Furthermore, 5-Methoxyflavone-stimulated downregulation of SREBP1/SCD signaling triggered ferroptosis in NPC cells by promoting iron accumulation, lipid peroxidation, and GSH depletion. Overexpression of SCD reversed the ferroptosis-inducing effects of 5-Methoxyflavone. Conclusions: Our findings reveal that 5-Methoxyflavone inhibits NPC proliferation by blocking lipid synthesis and inducing ferroptosis via the p53/SREBPs/SCD signaling pathway, providing evidence for the development of innovative drugs for NPC treatment. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12896-026-01163-9.
SN - 1472-6750
ER -