Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells
Abstract Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthes...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Journal of Ovarian Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13048-024-01389-1 |
| _version_ | 1797219654607831040 |
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| author | Juwon Lee Suin Jang Jihye Im Youngjin Han Soochi Kim HyunA Jo Wenyu Wang Untack Cho Se Ik Kim Aeran Seol Boyun Kim Yong Sang Song |
| author_facet | Juwon Lee Suin Jang Jihye Im Youngjin Han Soochi Kim HyunA Jo Wenyu Wang Untack Cho Se Ik Kim Aeran Seol Boyun Kim Yong Sang Song |
| author_sort | Juwon Lee |
| collection | DOAJ |
| description | Abstract Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis. |
| first_indexed | 2024-04-24T12:37:05Z |
| format | Article |
| id | doaj.art-3b0c54992f8c43b0b925bf7c596656d2 |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-24T12:37:05Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-3b0c54992f8c43b0b925bf7c596656d22024-04-07T11:27:11ZengBMCJournal of Ovarian Research1757-22152024-04-0117111310.1186/s13048-024-01389-1Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cellsJuwon Lee0Suin Jang1Jihye Im2Youngjin Han3Soochi Kim4HyunA Jo5Wenyu Wang6Untack Cho7Se Ik Kim8Aeran Seol9Boyun Kim10Yong Sang Song11WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National UniversityCancer Research Institute, College of Medicine, Seoul National UniversityCancer Research Institute, College of Medicine, Seoul National UniversityCancer Research Institute, College of Medicine, Seoul National UniversityDepartment of Neurology and Neurological Sciences, Stanford University School of MedicineWCU Biomodulation, Department of Agricultural Biotechnology, Seoul National UniversityDepartment of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang UniversityCancer Research Institute, College of Medicine, Seoul National UniversityDepartment of Obstetrics and Gynecology, College of Medicine, Seoul National UniversityDepartment of Obstetrics and Gynecology, College of Medicine, Seoul National UniversityDepartment of SmartBio, College of Life and Health Science, Kyungsung UniversityWCU Biomodulation, Department of Agricultural Biotechnology, Seoul National UniversityAbstract Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis.https://doi.org/10.1186/s13048-024-01389-1Ovarian cancerLipid metabolismSCD1ER stressApoptosis |
| spellingShingle | Juwon Lee Suin Jang Jihye Im Youngjin Han Soochi Kim HyunA Jo Wenyu Wang Untack Cho Se Ik Kim Aeran Seol Boyun Kim Yong Sang Song Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells Journal of Ovarian Research Ovarian cancer Lipid metabolism SCD1 ER stress Apoptosis |
| title | Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells |
| title_full | Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells |
| title_fullStr | Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells |
| title_full_unstemmed | Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells |
| title_short | Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells |
| title_sort | stearoyl coa desaturase 1 inhibition induces er stress mediated apoptosis in ovarian cancer cells |
| topic | Ovarian cancer Lipid metabolism SCD1 ER stress Apoptosis |
| url | https://doi.org/10.1186/s13048-024-01389-1 |
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