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
CNS activity of swertiamarin, a secoiridoid glucoside from Swertia chirata, was evaluated. An apparent anomaly, associated with the unanticipated finding that the alcoholic extracts (excluding mangiferin) of S. chirata significantly reversed the mangiferin-induced CNS-stimulating effects in albino mice and rats, was resolved. The results indicate that swertiamarin and mangiferin antagonize each other in vivo and thereby reverse their CNS effects.