DHEA inhibits proliferation, migration and alters mesenchymal-epithelial transition proteins through the PI3K/Akt pathway in MDA-MB-231 cells.

Colín-Val, Zaira; López-Díazguerrero, Norma Edith; López-Marure, Rebeca

Colín-Val, Zaira; López-Díazguerrero, Norma Edith; López-Marure, Rebeca.

Afiliação

Colín-Val Z; Departamento de Fisiología, Instituto Nacional de Cardiología "Ignacio Chávez", Ciudad de México, Mexico; Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Mexico.
López-Díazguerrero NE; Laboratorio de Bioenergética y Envejecimiento Celular, Departamento de Ciencias de la Salud, UAM-I, Mexico.
López-Marure R; Departamento de Fisiología, Instituto Nacional de Cardiología "Ignacio Chávez", Ciudad de México, Mexico. Electronic address: rebeca.lopez@cardiologia.org.mx.

J Steroid Biochem Mol Biol ; 208: 105818, 2021 04.

Article em En | MEDLINE | ID: mdl-33508440

RESUMO

Cancer is one of the leading causes of death worldwide, and breast cancer is the most common among women. Dehydroepiandrosterone (DHEA), the most abundant steroid hormone in human serum, inhibits proliferation and migration of breast cancer cells, modulating the expression of proteins involved in mesenchymal-epithelial transition (MET). However, the underlying molecular mechanisms are not fully understood. DHEA effects on the triple-negative breast cancer cell line MDA-MB-231 (mesenchymal stem-like) could be exerted by binding to receptors tyrosine kinase (RTKs) and signaling through MEK/ERK and/or PI3K/Akt pathways. In this study, MDA-MB-231 cells were exposed to DHEA in the presence of pharmacological inhibitors of these pathways and a siRNA against PIK3CA gene, which blocks PI3K pathway. Cell proliferation was measured by crystal violet staining, migration by the wound healing and transwell assays, and MET protein expression by western blot. A xenograft tumor growth in nude mice (nu-/nu-) using a siRNA against PI3K was also performed. Results showed that neither of the inhibitors used reverted the antiproliferative activity of DHEA. However, wortmannin and LY294002, inhibitors of the PI3K/Akt pathway, abolished the up- and down-regulation of E- and N-cadherin expression respectively, and inhibition of migration induced by DHEA in MDA-MB-231 cells. The siRNA that blocks the PI3K pathway, abolished the effects of DHEA on proliferation, migration, MET proteins expression and the growth of tumors in nude mice. In conclusion, these results suggest that PI3K/Akt pathway participates in the effects of DHEA on breast cancer cells.

Assuntos

Proliferação de Células/efeitos dos fármacos; Desidroepiandrosterona/farmacologia; Transição Epitelial-Mesenquimal/genética; Neoplasias de Mama Triplo Negativas/tratamento farmacológico; Animais; Caderinas/genética; Diferenciação Celular/efeitos dos fármacos; Linhagem Celular Tumoral; Movimento Celular/efeitos dos fármacos; Transição Epitelial-Mesenquimal/efeitos dos fármacos; Feminino; Humanos; Camundongos; Fosfatidilinositol 3-Quinases/genética; Proteínas Proto-Oncogênicas c-akt/genética; Transdução de Sinais/efeitos dos fármacos; Neoplasias de Mama Triplo Negativas/genética; Neoplasias de Mama Triplo Negativas/patologia; Ensaios Antitumorais Modelo de Xenoenxerto

Palavras-chave

Breast cancer cells; DHEA; Mesenchymal-epithelial transition; PI3K/Akt

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Desidroepiandrosterona / Proliferação de Células / Transição Epitelial-Mesenquimal / Neoplasias de Mama Triplo Negativas Limite: Animals / Female / Humans Idioma: En Revista: J Steroid Biochem Mol Biol Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: México País de publicação: Reino Unido

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