Cannabidiol attenuates lipid metabolism and induces CB1 receptor-mediated ER stress associated apoptosis in ovarian cancer cells
Abstract Ovarian cancer (OC) is the most deadly gynecological tumor. OC cells utilize cellular metabolic reprogramming to gain a survival advantage, particularly through aberrant lipid metabolic process. As the primary ingredient in exogenous cannabinoids, cannabidiol (CBD) has been confirmed to exh...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-88917-1 |
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| author | Xuanhe Fu Zhixiong Yu Fang Fang Weiping Zhou Yuxin Bai Zhongjia Jiang Biao Yang Ye Sun Xing Tian Guangyan Liu |
| author_facet | Xuanhe Fu Zhixiong Yu Fang Fang Weiping Zhou Yuxin Bai Zhongjia Jiang Biao Yang Ye Sun Xing Tian Guangyan Liu |
| author_sort | Xuanhe Fu |
| collection | DOAJ |
| description | Abstract Ovarian cancer (OC) is the most deadly gynecological tumor. OC cells utilize cellular metabolic reprogramming to gain a survival advantage, particularly through aberrant lipid metabolic process. As the primary ingredient in exogenous cannabinoids, cannabidiol (CBD) has been confirmed to exhibit antitumor activity in preclinical studies. However, it is still unclear whether CBD can disrupt fatty acid metabolism and induce apoptosis in OC cells. In this study, we have demonstrated that CBD significantly inhibits the proliferation of OCs through a cannabinoid receptor type 1 (CB1R)-mediated manner. Fatty acid metabolic profiling and flow cytometry analysis revealed that CBD has the ability to decrease fatty acid levels and significantly suppress the transcription of genes involved in fatty acid uptake and synthesis in ES-2 cells. In addition, the analysis from RNA-seq and real-time RT-PCR revealed that CBD activated the endoplasmic reticulum (ER) stress pathway. Conversely, by supplementation with unsaturated fatty acid or blocking CB1R, ER stress or reactive oxygen species (ROS) signals with specific inhibitors could significantly relieve CBD induced, dose-dependent, ER stress associated apoptosis, G0-G1 phase arrest, and mitochondrial dysfunction. Taken collectively, these data indicate that CBD may disrupt lipid metabolism, and lead to ER stress-related apoptosis in OCs. Our findings may provide a theoretical mechanism for anti-ovarian cancer using CBD. |
| format | Article |
| id | doaj-art-3edbe20f0f4e4d40930276bc7a34ce3d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-3edbe20f0f4e4d40930276bc7a34ce3d2025-02-09T12:31:47ZengNature PortfolioScientific Reports2045-23222025-02-0115111610.1038/s41598-025-88917-1Cannabidiol attenuates lipid metabolism and induces CB1 receptor-mediated ER stress associated apoptosis in ovarian cancer cellsXuanhe Fu0Zhixiong Yu1Fang Fang2Weiping Zhou3Yuxin Bai4Zhongjia Jiang5Biao Yang6Ye Sun7Xing Tian8Guangyan Liu9Department of Immunology, Shenyang Medical CollegeDepartment of Pathogen Biology, Shenyang Medical CollegeDepartment of Pathogen Biology, Shenyang Medical CollegeDepartment of Pathogen Biology, Shenyang Medical CollegeDepartment of Pathogen Biology, Shenyang Medical CollegeDepartment of Biochemistry and Molecular Biology, Shenyang Medical CollegeDepartment of Pathogen Biology, Shenyang Medical CollegeDepartment of Pathogen Biology, Shenyang Medical CollegeDepartment of Physiology, Shenyang Medical CollegeKey Lab of Environmental Pollution and Microecology of Liaoning ProvinceAbstract Ovarian cancer (OC) is the most deadly gynecological tumor. OC cells utilize cellular metabolic reprogramming to gain a survival advantage, particularly through aberrant lipid metabolic process. As the primary ingredient in exogenous cannabinoids, cannabidiol (CBD) has been confirmed to exhibit antitumor activity in preclinical studies. However, it is still unclear whether CBD can disrupt fatty acid metabolism and induce apoptosis in OC cells. In this study, we have demonstrated that CBD significantly inhibits the proliferation of OCs through a cannabinoid receptor type 1 (CB1R)-mediated manner. Fatty acid metabolic profiling and flow cytometry analysis revealed that CBD has the ability to decrease fatty acid levels and significantly suppress the transcription of genes involved in fatty acid uptake and synthesis in ES-2 cells. In addition, the analysis from RNA-seq and real-time RT-PCR revealed that CBD activated the endoplasmic reticulum (ER) stress pathway. Conversely, by supplementation with unsaturated fatty acid or blocking CB1R, ER stress or reactive oxygen species (ROS) signals with specific inhibitors could significantly relieve CBD induced, dose-dependent, ER stress associated apoptosis, G0-G1 phase arrest, and mitochondrial dysfunction. Taken collectively, these data indicate that CBD may disrupt lipid metabolism, and lead to ER stress-related apoptosis in OCs. Our findings may provide a theoretical mechanism for anti-ovarian cancer using CBD.https://doi.org/10.1038/s41598-025-88917-1Ovarian cancerLipid metabolismCannabidiol |
| spellingShingle | Xuanhe Fu Zhixiong Yu Fang Fang Weiping Zhou Yuxin Bai Zhongjia Jiang Biao Yang Ye Sun Xing Tian Guangyan Liu Cannabidiol attenuates lipid metabolism and induces CB1 receptor-mediated ER stress associated apoptosis in ovarian cancer cells Scientific Reports Ovarian cancer Lipid metabolism Cannabidiol |
| title | Cannabidiol attenuates lipid metabolism and induces CB1 receptor-mediated ER stress associated apoptosis in ovarian cancer cells |
| title_full | Cannabidiol attenuates lipid metabolism and induces CB1 receptor-mediated ER stress associated apoptosis in ovarian cancer cells |
| title_fullStr | Cannabidiol attenuates lipid metabolism and induces CB1 receptor-mediated ER stress associated apoptosis in ovarian cancer cells |
| title_full_unstemmed | Cannabidiol attenuates lipid metabolism and induces CB1 receptor-mediated ER stress associated apoptosis in ovarian cancer cells |
| title_short | Cannabidiol attenuates lipid metabolism and induces CB1 receptor-mediated ER stress associated apoptosis in ovarian cancer cells |
| title_sort | cannabidiol attenuates lipid metabolism and induces cb1 receptor mediated er stress associated apoptosis in ovarian cancer cells |
| topic | Ovarian cancer Lipid metabolism Cannabidiol |
| url | https://doi.org/10.1038/s41598-025-88917-1 |
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