RESUMO
Tomatoes may protect against prostate cancer development, possibly through targeting signaling pathways such as nuclear factor-κB (NF-κB). We investigated whether tomato paste could modulate NF-κB activity and cancer-related gene expression in human derived prostate cancer cells (PC3) and PC3 xenografts. PC3-cells were stably transduced with an NF-κB-luciferase construct, and treated with tomato extracts or vehicle control. Nude mice bearing PC3 xenografts were fed a Western-like diet with or without 10% tomato paste for 6.5 wk. The tomato diet significantly inhibited TNFα stimulated NF-κB activity in cultured PC3 cells, and modulated the expression of genes associated with inflammation, apoptosis, and cancer progression. Accumulation of lycopene occurred in liver, xenografts, and serum of mice fed tomato diet. Tomato paste in the diet did not affect tumor size in mice; however, there was a trend toward inhibition of NF-κB activity in the xenografts. The effect of tomato on gene expression was most prominent in the xenograft microenvironment, where among others NFKB2, STAT3, and STAT6 showed higher expression levels after tomato treatment. Our findings support biological activity of tomatoes in cancer-related inflammation.
Assuntos
NF-kappa B/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neoplasias da Próstata/metabolismo , RNA Mensageiro/efeitos dos fármacos , Solanum lycopersicum/química , Animais , Carotenoides/análise , Carotenoides/metabolismo , Carotenoides/farmacologia , Linhagem Celular Tumoral , Expressão Gênica , Perfilação da Expressão Gênica , Xenoenxertos/efeitos dos fármacos , Humanos , Licopeno , Masculino , Camundongos , Camundongos Nus , NF-kappa B/genética , NF-kappa B/metabolismo , Oxirredução , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/efeitos dos fármacos , Fator de Transcrição STAT6/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
The CC chemokine eotaxin contributes to epithelium-induced inflammation in airway diseases such as asthma. Eupatilin (5,7-dihydroxy-3',4',6'-trimethoxyflavone), a bioactive component of Artemisia asiatica Nakai (Asteraceae), is reported to inhibit the adhesion of eosinophils to bronchial epithelial cells. However, little is known about the molecular mechanism of eupatilin-induced attenuation of bronchial epithelium-induced inflammation. In this study, we investigated the effect of eupatilin on expression of eotaxin-1 (CCL11), a potent chemoattractant for eosinophils. Eupatilin significantly inhibited eotaxin expression in bronchial epithelial cells stimulated with TNF-α, while NF-κB and IκBα kinase (IKK) activities declined concurrently. Eupatilin also inhibited mitogen-activated protein kinase (MAPK) activity; however, all of these anti-inflammatory activities were reversed by MAPK overexpression. In contrast, eupatilin did not affect the signal transducer and activator of transcription 6 (STAT6) signalling in bronchial epithelial cells stimulated with IL-4. Furthermore, eupatilin significantly attenuated TNF-α-induced eosinophil migration. These results suggest that the eupatilin inhibits the signalling of MAPK, IKK, NF-κB and eotaxin-1 in bronchial epithelial cells, leading to inhibition of eosinophil migration.