Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells

Abstract: The aim of this study was to study the effects of human umbilical cord mesenchymal stem cells (HUC-MSCs) on glutathione (GSH) metabolism in human ovarian cancer cells induced by phosphoramide mustard (PM). The experiment was divided into five groups, namely, the blank group (ovarian cancer cells), the control group (ovarian cancer cells + HUC-MSCs), the model group (ovarian cancer cells + PM), the treatment group (ovarian cancer cells + PM + HUC-MSCs), and the inhibitor group (ovarian cancer cells + PM + HUC-MSCs + extracellular signal-regulated protein kinase inhibitor PD98059). The apoptosis rate of ovarian cancer cells was detected by flow cytometry. Intracellular levels of oxidized glutathione (GSSG), GSH, γ-glutamyl cysteine synthetase (γ-GCS), and intracellular reactive oxygen species (ROS) were detected by enzyme-linked immunosorbent assay. Protein imprinting and real-time fluorescence quantitative PCR were used to detect extracellular regulated protein kinase (ERK), p-ERK heme oxygenase-1 (HO-1), and nuclear factor E2-related factor 2 (Nrf2) protein levels. First, the apoptosis rate in the model group was increased compared with that of the blank group. The levels of γ-GCS, p-ERK, HO-1, and Nrf-2 decreased, while the levels of malondialdehyde, GSSG, and ROS increased. Second, compared with the model group, the apoptosis rate in the treatment group decreased. GSH, γ-GCS, p-ERK, HO-1, and Nrf2 levels increased. Malondialdehyde, GSSG, and ROS levels decreased. Third, after the administration of ERK inhibitor, the apoptosis rate of cells increased. GSH, p-ERK, and HO-1 levels decreased. GSSG and ROS levels increased (P < 0.05), and γ-GCS level had a downward trend compared with the treatment group. To conclude, HUC-MSCs may regulate the ERK–Nrf2–HO-1 pathway to increase γ-GCS expression and GSH production, reduce ROS level and apoptosis of ovarian cancer cells, and improve antioxidant capacity.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells ; volume:19 ; number:1 ; year:2024 ; extent:15
Open life sciences ; 19, Heft 1 (2024) (gesamt 15)

Creator
Sun, Lu
Fan, Xiaodong
Chen, Qian
Liu, Guoyan

DOI
10.1515/biol-2022-0997
URN
urn:nbn:de:101:1-2411211623577.729011560924
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
15.08.2025, 7:24 AM CEST

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Associated

  • Sun, Lu
  • Fan, Xiaodong
  • Chen, Qian
  • Liu, Guoyan

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