Journal Article

Lycopene and Beta-Carotene Induce Growth Inhibition and Proapoptotic Effects on ACTH-Secreting Pituitary Adenoma Cells

Soares, Nathália, Gomes, Flávia Carvalho Alcântara, Haddad, Natália F., Nasciutti, Luiz Eurico, Dezonne, Rômulo Sperduto, de Carvalho, Denise Pires, de Mattos, Rômulo Medina, Leite de Oliveira, Felipe, Vairo, Leandro, Miranda-Alves, Leandro, Teodoro, Anderson J., Goldenberg, Regina Coeli dos Santos, Gadelha, Mônica R., Hecht, Fábio

2013

Overview

Pituitary adenomas comprise approximately 10-15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27(kip1) in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2) and increased expression of p27(kip1) in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27(kip1); and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing's disease.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenoma / Adenoma - pathology / Adrenocorticotropic hormone / Adrenocorticotropic Hormone - metabolism / Animals / Apoptosis / Apoptosis - drug effects / Beta carotene / beta Carotene - pharmacology / Biology / Brain cancer / Cancer prevention / Cancer research / Carotene / Carotenoids / Carotenoids - pharmacology / Cell cycle / Cell Cycle - drug effects / Cell growth / Cell interactions / Cell Line, Tumor / Cell Proliferation - drug effects / Cell signaling / Cell Survival - drug effects / Chronic diseases / Communication / Compression / Connexin 43 / Connexin 43 - metabolism / Corticotropin / Cushing syndrome / Cushing's disease / Cyclin-dependent kinase inhibitor p27 / Cyclin-Dependent Kinase Inhibitor p27 - metabolism / Functional foods / Functional foods & nutraceuticals / Gap Junctions - drug effects / Gap Junctions - metabolism / Gene expression / Growth inhibition / Health risks / Hospitals / Kinases / Lycopene / Medical treatment / Medicine / Mice / Morbidity / Nervous system diseases / Pharmacology / Phosphorylation / Phosphorylation - drug effects / Pituitary / Pituitary gland / Pituitary Neoplasms - pathology / Pituitary tumors / Proteins / Rodents / S-Phase Kinase-Associated Proteins - metabolism / Secretion / Studies / Tumors / Vitamin A