Unveiling the Anticancer Potential of Urolithin A in Colorectal Cancer:A Systematic ReviewOA
Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer effects of Uro-A in CRC,highlighting effective concentration ranges,exposure times,relevant outcomes,and underlying molecular mechanisms.Methods:Following PRISMA 2020 guidelines,a systematic search was conducted in PubMed,Scopus,and Web of Science using the following strategy:(colorectal cancer)AND(urolithin a)OR(3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one).Eligibility criteria were defined by the PICO framework:(P)in vitro CRC cell models;(I)Uro-A alone or combined treatments;(C)No intervention,vehicle or other treatments;(O)Relevant anticancer outcomes of Uro-A in CRC.Only original,full-text,in vitro studies in English were included.Risk of bias was assessed using ToxRTool.A qualitative synthesis was performed due to the heterogeneity of the included studies.Results:Fifteen studies met inclusion criteria,involving CRC cell lines(Caco-2,HCT-116,HT-29,SW480,SW620)and normal colon fibroblasts(CCD18-Co).Uro-A inhibited CRC cell proliferation,clonogenic growth,cancer stem cells properties,migration,and invasion,and induced cell cycle arrest,apoptosis,autophagy,and senescence,through modulation of key signaling pathways and proteins.Co-treatments with conventional chemotherapeutics and microbiota-derived metabolites showed additive or synergistic effects.Discussion:The findings support UroA’s potential as a preventive or adjuvant agent in CRC treatment.However,preclinical nature of the evidence and methodological heterogeneity hinder clinical extrapolation to in vivo contexts.Human clinical trials are necessary to overcome these limitations.Other:This review was registered in PROSPERO(CRD420251070874)and supported by FCT/MCTES UIDP/05608/2020 and UIDB/05608/2020.Institutional.
Mariana Francisco;Fernando Mendes;Diana Martins;Joana Liberal
Polytechnic University of Coimbra,ESTESC,UCPCBL,Rua 5 de Outubro,SM Bispo,Apartado,Coimbra,3046-854,PortugalPolytechnic University of Coimbra,ESTESC,UCPCBL,Rua 5 de Outubro,SM Bispo,Apartado,Coimbra,3046-854,Portugal H&TRC—Health&Technology Research Center,Coimbra Health School,Polytechnic University of Coimbra,Coimbra,3045-043,Portugal Coimbra Institute for Clinical and Biomedical Research(iCBR)Area of Environment Genetics and Oncobiology(CIMAGO),Biophysics Institute of Faculty of Medicine,University of Coimbra,Coimbra,3045-043,Portugal Center for Innovative Biomedicine and Biotechnology(CIBB),University of Coimbra,Coimbra,3045-043,Portugal European Association of Biomedical Scientists,Brussels,1000,BelgiumPolytechnic University of Coimbra,ESTESC,UCPCBL,Rua 5 de Outubro,SM Bispo,Apartado,Coimbra,3046-854,Portugal H&TRC—Health&Technology Research Center,Coimbra Health School,Polytechnic University of Coimbra,Coimbra,3045-043,Portugal Coimbra Institute for Clinical and Biomedical Research(iCBR)Area of Environment Genetics and Oncobiology(CIMAGO),Biophysics Institute of Faculty of Medicine,University of Coimbra,Coimbra,3045-043,Portugal Center for Innovative Biomedicine and Biotechnology(CIBB),University of Coimbra,Coimbra,3045-043,PortugalPolytechnic University of Coimbra,ESTESC,UCPCBL,Rua 5 de Outubro,SM Bispo,Apartado,Coimbra,3046-854,Portugal H&TRC—Health&Technology Research Center,Coimbra Health School,Polytechnic University of Coimbra,Coimbra,3045-043,Portugal
医药卫生
Colorectal cancerurolithin A3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-oneanticancer effectssystematic review
《Oncology Research》 2026 (2)
P.54-89,36
supported by FCT/MCTES UIDP/05608/2020(https://doi.org/10.54499/UIDP/05608/2020,accessed on 01 July 2025)UIDB/05608/2020(https://doi.org/10.54499/UIDB/05608/2020,accessed on 01 July 2025).Institutional.
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