Abstract
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 p27kip1 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 p27kip1 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 p27kip1; and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing’s disease.
Highlights
Dysfunction of the pituitary gland can be caused by a wide variety of diseases such as hypopituitarism and tumors, which may produce major clinical manifestations
The treatment of lycopene for 48 and 96 h induced an inhibition of cell viability from the concentration of 2.5 mM, and the maximum inhibition was obtained with 40 mM (30%, p,0.01) (Figures 1A and 1B)
It has recently been reported that the use of pasireotide, a somatostatin analogue, has shown success in treating this disease [23,24]
Summary
Dysfunction of the pituitary gland can be caused by a wide variety of diseases such as hypopituitarism and tumors, which may produce major clinical manifestations. Pituitary adenomas are probably much more common than previously assumed; their prevalence is roughly 1 per 1000 people [1,2]. These tumors have a monoclonal origin and are classified as endocrine-active or -inactive adenomas, whereas pituitary carcinomas are extremely rare [3]. They do result in morbidity caused by altered hormonal patterns, therapeutic side effects, and compression of adjacent sella turcica structures [4,5,6].
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