Essential Oils from Citrus Peels Promote Calcium Overload-Induced Calcicoptosis in U251 Cells
Citrus peel essential oils (CPEOs) have demonstrated substantial medicinal potential for glioblastoma treatment because of their extensive antitumor effects, low potential for drug resistance, and ability to cross the human blood–brain barrier. In this study, the chemical compositions of five CPEOs...
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2024-12-01
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| Series: | Antioxidants |
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| author | Yurong Li Juanjuan Wei Zimao Ye Chen Ji Wenji Li Li Xu Zhiqin Zhou |
| author_facet | Yurong Li Juanjuan Wei Zimao Ye Chen Ji Wenji Li Li Xu Zhiqin Zhou |
| author_sort | Yurong Li |
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| description | Citrus peel essential oils (CPEOs) have demonstrated substantial medicinal potential for glioblastoma treatment because of their extensive antitumor effects, low potential for drug resistance, and ability to cross the human blood–brain barrier. In this study, the chemical compositions of five CPEOs were analyzed via gas chromatography–mass spectrometry (GC-MS). CCK8 assays were used to evaluate the ability of five CPEOs to inhibit U251 human glioblastoma cells, and XLB and RA were selected for further investigation. Through wound healing assays and cell cycle and apoptosis analyses via flow cytometry, it was revealed that these CPEOs inhibited cell migration, arrested the cell cycle at G1/G0, and induced apoptosis with similar levels of inhibition. After CPEOs treatment, the intracellular Ca<sup>2+</sup> content and reactive oxygen species levels in U251 cells increased significantly, whereas the mitochondrial membrane potential decreased. Additionally, the antioxidant enzyme system (SOD, POD, CAT, and GR) and the nonenzymatic defense system (GSH) were inhibited, leading to an increase in lipid peroxidation. qRT–PCR indicated the significant upregulation of intracellular calcium ion signaling pathways and the upregulation of mitochondrial apoptosis-related genes. Additionally, the activation of calcicoptosis-related indicators induced by the CPEOs could be reversed by inhibitor treatment, confirming that both of the selected CPEOs inhibit tumors by activating calcicoptosis-related pathways. These findings highlight the immense potential of CPEOs in healthcare and pharmaceutical applications by not only providing a scientific basis for the potential application of CPEOs in the treatment of glioblastoma but also offering new insights for the development of novel antitumor drugs. |
| format | Article |
| id | doaj-art-55738845c50a49308612f7fd3434e047 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2024-12-01 |
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| series | Antioxidants |
| spelling | doaj-art-55738845c50a49308612f7fd3434e0472025-01-24T13:19:07ZengMDPI AGAntioxidants2076-39212024-12-011411110.3390/antiox14010011Essential Oils from Citrus Peels Promote Calcium Overload-Induced Calcicoptosis in U251 CellsYurong Li0Juanjuan Wei1Zimao Ye2Chen Ji3Wenji Li4Li Xu5Zhiqin Zhou6Key Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Horticulture and Landscape Architecture, Southwest University, Beibei District, Chongqing 400715, ChinaKey Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Horticulture and Landscape Architecture, Southwest University, Beibei District, Chongqing 400715, ChinaKey Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Horticulture and Landscape Architecture, Southwest University, Beibei District, Chongqing 400715, ChinaKey Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Horticulture and Landscape Architecture, Southwest University, Beibei District, Chongqing 400715, ChinaSchool of Design, Chongqing Industry Polytechnic College, Chongqing 401120, ChinaCollege of Sericulture, Textile and Biomass Sciences, Southwest University, Beibei District, Chongqing 400715, ChinaKey Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Horticulture and Landscape Architecture, Southwest University, Beibei District, Chongqing 400715, ChinaCitrus peel essential oils (CPEOs) have demonstrated substantial medicinal potential for glioblastoma treatment because of their extensive antitumor effects, low potential for drug resistance, and ability to cross the human blood–brain barrier. In this study, the chemical compositions of five CPEOs were analyzed via gas chromatography–mass spectrometry (GC-MS). CCK8 assays were used to evaluate the ability of five CPEOs to inhibit U251 human glioblastoma cells, and XLB and RA were selected for further investigation. Through wound healing assays and cell cycle and apoptosis analyses via flow cytometry, it was revealed that these CPEOs inhibited cell migration, arrested the cell cycle at G1/G0, and induced apoptosis with similar levels of inhibition. After CPEOs treatment, the intracellular Ca<sup>2+</sup> content and reactive oxygen species levels in U251 cells increased significantly, whereas the mitochondrial membrane potential decreased. Additionally, the antioxidant enzyme system (SOD, POD, CAT, and GR) and the nonenzymatic defense system (GSH) were inhibited, leading to an increase in lipid peroxidation. qRT–PCR indicated the significant upregulation of intracellular calcium ion signaling pathways and the upregulation of mitochondrial apoptosis-related genes. Additionally, the activation of calcicoptosis-related indicators induced by the CPEOs could be reversed by inhibitor treatment, confirming that both of the selected CPEOs inhibit tumors by activating calcicoptosis-related pathways. These findings highlight the immense potential of CPEOs in healthcare and pharmaceutical applications by not only providing a scientific basis for the potential application of CPEOs in the treatment of glioblastoma but also offering new insights for the development of novel antitumor drugs.https://www.mdpi.com/2076-3921/14/1/11citrusessential oilglioblastomacalcium overloadcalcicoptosis |
| spellingShingle | Yurong Li Juanjuan Wei Zimao Ye Chen Ji Wenji Li Li Xu Zhiqin Zhou Essential Oils from Citrus Peels Promote Calcium Overload-Induced Calcicoptosis in U251 Cells Antioxidants citrus essential oil glioblastoma calcium overload calcicoptosis |
| title | Essential Oils from Citrus Peels Promote Calcium Overload-Induced Calcicoptosis in U251 Cells |
| title_full | Essential Oils from Citrus Peels Promote Calcium Overload-Induced Calcicoptosis in U251 Cells |
| title_fullStr | Essential Oils from Citrus Peels Promote Calcium Overload-Induced Calcicoptosis in U251 Cells |
| title_full_unstemmed | Essential Oils from Citrus Peels Promote Calcium Overload-Induced Calcicoptosis in U251 Cells |
| title_short | Essential Oils from Citrus Peels Promote Calcium Overload-Induced Calcicoptosis in U251 Cells |
| title_sort | essential oils from citrus peels promote calcium overload induced calcicoptosis in u251 cells |
| topic | citrus essential oil glioblastoma calcium overload calcicoptosis |
| url | https://www.mdpi.com/2076-3921/14/1/11 |
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