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Administration of selective serotonin reuptake inhibitors (SSRIs) is associated with a reduced cancer risk and shows significant anti-tumor effects across multiple tumor types, suggesting the potential for repurposing SSRIs in cancer therapy. Nonetheless, the specific molecular target and mechanism of action of SSRIs remain to be fully elucidated. Here, we reveal that citalopram exerts an immune-dependent anti-tumor effect in hepatocellular carcinoma (HCC). Interestingly, the anti-HCC effects of citalopram are not reliant on its conventional target, the serotonin transporter. Through various drug repurposing approaches, including global reverse gene expression profiling, drug affinity responsive target stability assay, and molecular docking, the complement component 5a receptor 1 (C5aR1) is identified as a new target of citalopram. C5aR1 is predominantly expressed by tumor-associated macrophages, and citalopram treatment enhances local macrophage phagocytosis and elicits CD8+ T anti-tumor immunity. C5aR1 deficiency or depletion of CD8+ T cells hinders the anti-HCC effects of citalopram. Collectively, our study reveals the immunomodulatory roles of citalopram in inducing anti-tumor immunity and provides a basis for considering the repurposing of SSRIs as promising anticancer agents for HCC treatment.
Pubmed ID: 41661166
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Collection of information about chemical structures and biological properties of small molecules and siRNA reagents hosted by the National Center for Biotechnology Information (NCBI).
View all literature mentionsAs one of three primary databases of PubChem (Pcsubstance, Pccompound, and PCBioAssay), PubChem Substance Database contains descriptions of chemical samples, from a variety of sources, and links to PubMed citations, protein 3D structures, and biological screening results that are available in PubChem BioAssay. If the contents of a chemical sample are known, the description includes links to PubChem Compound. A PubChem FTP is available and new data is accepted into the repository. Pcsubstance contains more than 81 million records (2011).
View all literature mentionsThe National Natural Science Foundation of China (NSFC) is an organization directly affiliated to the State Council for the management of the National Natural Science Fund. # In accordance with the guiding principles, policies and plans for the development of science and technology in China and by adopting the operating mechanisms for the National Natural Science Fund which conform to the socialism market economic system, NSFC supports basic research and some of applied research, identifies and fosters talented researchers in the realm of science and technology, accelerates the progress of science and technology, and promotes the socioeconomic development in China by giving full play the guidance and coordinating role of the National Natural Science Fund from the central government. # NSFC is in charge of the management of the National Natural Science Fund. It compiles and promulgates the annual Guide to Programs for basic research and some of applied research, handles applications of research projects, and organizes peer review and select the best projects to support. It endeavors to create an academic environment conducive to innovation. # NSFC cooperates with the Ministry of Science and Technology to formulate the principles, policies and plans for the development of basic research in China. When entrusted, it provides consultation and undertakes related assignments on major issues for the development of high technology and applied research in China. # NSFC gives help and support to other Chinese foundations in natural sciences. # NSFC establishes contacts with governmental departments in charge of science and technology, science foundations and related academic organizations in other countries and carries out international cooperation and exchange. # NSFC is responsible for the administration, supervision and guidance of the subordinated bodies. # NSFC undertakes other tasks entrusted by the State Council and the State Leading Group for Science and Technology and Education.
View all literature mentionsMajor research university in Shanghai. Established on April 8, 1896, as Nanyang Public School by an imperial edict issued by the Guangxu Emperor, it is one of China's oldest universities.
View all literature mentionsSoftware suite of automated docking tools. Designed to predict how small molecules, such as substrates or drug candidates, bind to receptor of known 3D structure. AutoDock consist of AutoDock 4 and AutoDock Vina. AutoDock 4 consists of autodock to perform docking of ligand to set of grids describing target protein, and autogrid to pre calculate these grids.
View all literature mentionsCollection of structural data of biological macromolecules. Database of information about 3D structures of large biological molecules, including proteins and nucleic acids. Users can perform queries on data and analyze and visualize results.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsProvides digital infrastructure, data analytics and decision support tools to help in diagnosis, treatment and monitoring of patients.
View all literature mentionsEnhanced web server for large-scale expression profiling and interactive analysis. GEPIA2 is updated and enhanced version of GEPIA, offering more functionalities, higher resolution data analysis, and additional features like ability to analyze specific cancer subtypes, quantify gene signatures based on single-cell sequencing studies, and allow users to upload their own RNA-seq data for comparison with the TCGA and GTEx datasets; essentially providing more comprehensive and advanced platform for gene expression analysis compared to the original GEPIA version.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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