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Environ Toxicol Pharmacol ; 95: 103943, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35934220

RESUMO

Colorectal cancer (CRC) is a common malignancy with high mortality and poor prognosis. Diacerein (DIA) is an anti-inflammatory used for treatment of osteoarthritis. We delineated some underlying molecular mechanisms of DIA's anti-carcinogenic effect in CRC using in vivo and in vitro models. Human Caco-2 cells were treated with DIA followed by MTT and Annexin V assays and CRC was experimentally induced using 1,2-dimethylhydrazine. DIA (50 mg/kg/day, orally) was administrated for 8 weeks. The MTT assay confirmed cytotoxic effect of DIA in vitro and Annexin V confirmed its apoptotic effect. DIA resulted in regression of tumour lesions with reduced colonic TLR4, NF-κB and TNF-α protein levels and down-regulated VEGF expression, confirming anti-angiogenic impact. DIA triggered caspase-3 expression and regulated Wnt/ß-Catenin pathway, by apparently interrupting the IL-6/STAT3/ lncRNA HOTAIR axis. In conclusion, DIA disrupted IL-6/STAT3/ lncRNA HOTAIR axis which could offer an effective therapeutic strategy for the management of CRC.


Assuntos
Anticarcinógenos , RNA Longo não Codificante , 1,2-Dimetilidrazina/metabolismo , 1,2-Dimetilidrazina/farmacologia , Anexina A5 , Antraquinonas , Anti-Inflamatórios/farmacologia , Anticarcinógenos/farmacologia , Células CACO-2 , Carcinogênese/metabolismo , Caspase 3/metabolismo , Proliferação de Células , Colo , Humanos , Interleucina-6/metabolismo , NF-kappa B/metabolismo , RNA Longo não Codificante/genética , Fator de Transcrição STAT3 , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo
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