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Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells.
Lee, Juwon; Jang, Suin; Im, Jihye; Han, Youngjin; Kim, Soochi; Jo, HyunA; Wang, Wenyu; Cho, Untack; Kim, Se Ik; Seol, Aeran; Kim, Boyun; Song, Yong Sang.
Afiliación
  • Lee J; WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
  • Jang S; Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.
  • Im J; Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.
  • Han Y; Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.
  • Kim S; Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.
  • Jo H; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Wang W; Paul F. Glenn Laboratories for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Cho U; WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
  • Kim SI; Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.
  • Seol A; Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
  • Kim B; Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.
  • Song YS; Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
J Ovarian Res ; 17(1): 73, 2024 Apr 02.
Article en En | MEDLINE | ID: mdl-38566208
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Estearoil-CoA Desaturasa Límite: Female / Humans Idioma: En Revista: J Ovarian Res Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Estearoil-CoA Desaturasa Límite: Female / Humans Idioma: En Revista: J Ovarian Res Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido