National Institute of Health Dr. Ricardo Jorge
Repositório Científico do Instituto Nacional de SaúdeNot a member yet
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Arquivos do Instituto Nacional de Saúde
Full text linkContinuação de: Boletim do Instituto Superior de Higiene Doutor Ricardo Jorg
Boletim do Instituto Superior de Higiene Doutor Ricardo Jorge
Full text linkContinuação de: Arquivos do Instituto Central de HigieneContinuado por: Arquivos do Instituto Nacional de Saúd
Arquivos do Instituto Central de Higiene. Secção de demografia e estatística
No full textContinuação de: Annaes de Saude Publica do Reino. Secção de demographia e estatística (1906)Continuado por: Boletim do Instituto Superior de Higiene Doutor Ricardo Jorg
Arquivos do Instituto Central de Higiene. Secção de higiene
Full text linkSubstitui: Annaes de Saude Publica do Reino. Secção de higieneContinuado por: Boletim do Instituto Superior de Higiene Doutor Ricardo Jorg
Arquivos do Instituto Central de Higiene. Secção de legislação
No full textContinua em parte: Boletim dos Serviços Sanitários do ReinoContinuado por: Boletim do Instituto Superior de Higiene Doutor Ricardo Jorg
Estrogen-mediated inhibition of purine metabolism and cell cycle arrest as a novel therapeutic approach in colorectal cancer
No full textPurine metabolism is upregulated in various cancers including colorectal cancer (CRC). While previous work has elucidated the role of estrogen (E2) in metabolic reprogramming and ATP production, the effect of E2 on purine metabolism remains largely unknown. Herein, the impact of E2 signalling on purine metabolism in CRC cells was investigated using metabolome and transcriptome profiling of cell extracts derived from E2-treated HCT-116 cells with intact or silenced estrogen receptor alpha (ERα). Purine metabolic pathway enrichment analysis showed that 27 genes in the de novo purine synthesis pathway were downregulated in E2-treated CRC cells. Downstream consequences of E2 treatment including the induction of DNA damage, cell cycle arrest, and apoptosis were all shown to be ERα-dependent. These findings demonstrate, for the first time, that E2 exerts a significant anti-growth and survival effect in CRC cells by targeting the purine synthesis pathway in a ERα-dependent manner, meriting further investigation of the therapeutic utility of E2 signalling in CRC.Highlights: - E2 downregulates 27 genes in CRC purine synthesis via ERα. - E2-induced DNA damage is ERα-dependent in CRC cells. - E2 causes cell cycle arrest in CRC cells through ERα. - Apoptosis in CRC cells is triggered by E2 via ERα. - E2 inhibits CRC cell growth by targeting purine metabolism.J.S.M. is funded by the King Hussein Cancer Foundation, Jordan (2022-KHA-001), and the Research Institute of Medical and Health Sciences, University of Sharjah (Project 23010901133)