RESUMO
Mango fruit contain many bioactive compounds, some of which are transcription factor regulators. Estrogen receptor alpha (ERα) and beta (ERß) are two regulators of gene transcription that are important in a variety of physiological processes and also in diseases including breast cancer. We examined the ability of the mango constituents quercetin, mangiferin, and the aglycone form of mangiferin, norathyriol, to activate both isoforms of the estrogen receptor. Quercetin and norathyriol decreased the viability of MCF-7 breast cancer cells whereas mangiferin had no effect on MCF-7 cells. We also determined that quercetin and mangiferin selectively activated ERα whereas norathyriol activated both ERα and ERß. Despite quercetin, mangiferin and norathyriol having similar polyphenolic structural motifs, only norathyriol activated ERß, showing that bioactive agents in mangoes have very specific biological effects. Such specificity may be important given the often-opposing roles of ERα and ERß in breast cancer proliferation and other cellular processes.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Receptor alfa de Estrogênio/agonistas , Fitoestrógenos/farmacologia , Quercetina/farmacologia , Xantenos/farmacologia , Xantonas/farmacologia , Animais , Antineoplásicos Fitogênicos/antagonistas & inibidores , Antineoplásicos Fitogênicos/metabolismo , Neoplasias da Mama/metabolismo , Células COS , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Antagonistas do Receptor de Estrogênio/farmacologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/agonistas , Receptor beta de Estrogênio/antagonistas & inibidores , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Frutas/química , Genes Reporter/efeitos dos fármacos , Humanos , Células MCF-7 , Mangifera/química , Proteínas de Neoplasias/agonistas , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fitoestrógenos/antagonistas & inibidores , Fitoestrógenos/metabolismo , Quercetina/antagonistas & inibidores , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Elementos de Resposta/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos , Xantenos/antagonistas & inibidores , Xantenos/metabolismo , Xantonas/antagonistas & inibidores , Xantonas/metabolismoRESUMO
Mangos are a source of bioactive compounds with potential health-promoting activity. This study evaluated the abilities of the mango components quercetin and mangiferin and the aglycone derivative of mangiferin, norathyriol, to modulate the transactivation of peroxisome proliferator-activated receptor isoforms (PPARs). PPARs are transcription factors important in many human diseases. Through the use of a gene reporter assay it was shown that quercetin inhibited the activation of all three isoforms of PPARs (PPARgamma IC(50) = 56.3 microM; PPARalpha IC(50) = 59.6 microM; PPARbeta IC(50) = 76.9 microM) as did norathyriol (PPARgamma IC(50) = 153.5 microM; PPARalpha IC(50) = 92.8 microM; PPARbeta IC(50) = 102.4 microM), whereas mangiferin did not inhibit the transactivation of any isoform. These findings suggest that mango components and metabolites may alter transcription and could contribute to positive health benefits via this or similar mechanisms.
