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
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), t...
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De Gruyter
2024-11-01
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| Online Access: | https://doi.org/10.1515/biol-2022-0997 |
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| author | Sun Lu Fan Xiaodong Chen Qian Liu Guoyan |
| author_facet | Sun Lu Fan Xiaodong Chen Qian Liu Guoyan |
| author_sort | Sun Lu |
| collection | DOAJ |
| description | 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. |
| format | Article |
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| institution | OA Journals |
| issn | 2391-5412 |
| language | English |
| publishDate | 2024-11-01 |
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| series | Open Life Sciences |
| spelling | doaj-art-23fda51b43634eb8bfbf0706fde456412025-08-20T01:53:30ZengDe GruyterOpen Life Sciences2391-54122024-11-01191604610.1515/biol-2022-0997Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cellsSun Lu0Fan Xiaodong1Chen Qian2Liu Guoyan3Department of Gynecology, Tianjin Medical University General Hospital, Tianjin, 300052, ChinaDepartment of Gynecology, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, 300100, ChinaDepartment of Ultrasonography, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, 300100, ChinaDepartment of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Huan hu xi Road, Hexi District, Tianjin, 300060, ChinaThe 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.https://doi.org/10.1515/biol-2022-0997premature ovarian insufficiencyphosphoramide mustardhuman umbilical cord mesenchymal stem cellsoxidative stressglutathionereactive oxygen speciesovarian cancer cells |
| spellingShingle | Sun Lu Fan Xiaodong Chen Qian Liu Guoyan 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 Open Life Sciences premature ovarian insufficiency phosphoramide mustard human umbilical cord mesenchymal stem cells oxidative stress glutathione reactive oxygen species ovarian cancer cells |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | premature ovarian insufficiency phosphoramide mustard human umbilical cord mesenchymal stem cells oxidative stress glutathione reactive oxygen species ovarian cancer cells |
| url | https://doi.org/10.1515/biol-2022-0997 |
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