2. Academic Validation
  3. CDDO-Me triggers ROS-dependent ferroptosis and apoptosis in cervical cancer via targeting PI3K/Nrf2 pathway

CDDO-Me triggers ROS-dependent ferroptosis and apoptosis in cervical cancer via targeting PI3K/Nrf2 pathway

  • Food Chem Toxicol. 2025 Oct:204:115664. doi: 10.1016/j.fct.2025.115664.
Wenxuan Li 1,  Mengying Wang 1,  Pan Du 1,  Anna Han 2,  Xinyue Feng 1,  Liyan Chen 3
Affiliations

Affiliations

  • 1 Key Laboratory of Pathobiology (Yanbian University), State Ethnic Affairs Commission, Yanji, 133000, PR China.
  • 2 Central Laboratory, Affiliated Hospital of Yanbian University, Yanji, Jilin, 133000, PR China.
  • 3 Key Laboratory of Pathobiology (Yanbian University), State Ethnic Affairs Commission, Yanji, 133000, PR China; Research and Innovation Group of Yanbian University, Yanbian University Medical College, Yanji, 133000, PR China. Electronic address: lychen@ybu.edu.cn.
PMID: 40714179 DOI: 10.1016/j.fct.2025.115664
Abstract

Context: Cervical Cancer (CC) ranks as one of the most common types of malignant tumors affecting women. CDDO-Me is derived from oleanolic acid, a pentacyclic triterpenoid obtained by chemical structural modification, which has been shown anti-tumor effects.

Results: CC cell proliferation was decreased by CDDO-Me both in vitro and in vivo. Mechanistically, CDDO-Me led to a reduction of intracellular mitochondrial volume and crista, or an increase of membrane density. The levels of ROS, Fe2+, MDA were increased while GSH was decreased. Meanwhile, the levels of protein expression of GPX4, Nrf2, NQO1 and FTH1 were observably inhibited by CDDO-Me. Specifically, Ferroptosis triggered by CDDO-Me was reverted by DFO. It has been demonstrated that CDDO-Me-induced Apoptosis and Ferroptosis in CC cells is contingent upon the PI3K/AKT-mediated Nrf2/NQO1 pathway.

Conclusions: CDDO-Me induces CC cell lines Apoptosis and Ferroptosis through the PI3K/Nrf2 signaling pathway, for exerting anti-proliferation effects.

Keywords

Apoptosis; CDDO-Me; Cervical cancer; Ferroptosis; PI3K/Nrf2 signaling pathway.

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