title: Stearoyl-CoA desaturase-1 mediated cell apoptosis in colorectal cancer by promoting ceramide synthesis.
abstract: Inhibition of stearoyl-CoA desaturase 1 (SCD1) has been found to effectively suppress tumor cell proliferation and induce apoptosis in numerous neoplastic lesions. However, mechanism underlying SCD1-mediated anti-tumor effect has maintained unclear. Herein, we reported endo-lipid messenger ceramides played a critical role in tumor fate modulated by SCD1 inhibition. In vitro study in colorectal cancer cells demonstrated inhibition of SCD1 activity promoted apoptosis attributed to mitochondria dysfunctions, upregulation of reaction oxygen species (ROS), alteration of mitochondrial transmembrane potential and translocation of mitochondrial protein cytochrome C. While these effects were mediated by intracellular ceramide signals through induction of ceramide biosynthesis, rather than exclusive SFA accumulation. In vivo study in xenograft colorectal cancer mice showed pharmacologic administration of SCD1 inhibitor A939 significantly delayed tumor growth, which was reversed by L-cycloserine, an inhibitor of ceramide biosynthesis. These results depicted the cross-talk of SCD1-mediated lipid pathway and endo-ceramide biosynthesis pathway, indicating roles of ceramide signals in SCD1-mediated anti-tumor property.
authors.affiliation: Medical College, Xiamen University, Xiamen, Fujian 361000, P. R. China.|Clinical Research Institute, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421000, P. R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Medical College, Xiamen University, Xiamen, Fujian 361000, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: Medical College, Xiamen University, Xiamen, Fujian 361000, P. R. China.|Engineering Research Center of Marine Biological Resource Comprehensive Utilization, Third Institute of Oceanography, State Oceanic Administration, Xiamen, Fujian 361000, P. R. China.
authors.forename: Longhe
authors.initials: L
authors.lastname: Yang
authors.affiliation: Medical College, Xiamen University, Xiamen, Fujian 361000, P. R. China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Li
authors.affiliation: Medical College, Xiamen University, Xiamen, Fujian 361000, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Fu
authors.affiliation: Medical College, Xiamen University, Xiamen, Fujian 361000, P. R. China.
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P. R. China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou, Fujian 350001, P. R. China.
authors.forename: Funan
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Medical College, Xiamen University, Xiamen, Fujian 361000, P. R. China.
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Medical College, Xiamen University, Xiamen, Fujian 361000, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002518:Ceramides / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002518:Ceramides; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase
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