Lycopene and beta-carotene induce growth inhibition and proapoptotic effects on ACTH-secreting pituitary adenoma cells
Authors: Rômulo Medina de Mattos
Flávia Carvalho Alcântara Gomes
Leandro Miranda-Alves
Anderson J Teodoro
Fábio Hecht
Rômulo Sperduto Dezonne
Leandro Vairo
Luiz Eurico Nasciutti
Denise Pires de Carvalho
Felipe Leite de Oliveira
Mônica R Gadelha
Regina Coeli Dos Santos Goldenberg
Nathália Soares
Natália F Haddad
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Pituitary adenomas; Carotenoids; Cell viability; Colony formation; Cell cycle
Affiliations: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil.

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 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. 

Retracted: No

PubPeer comments:
 February 2016 correction, at https: journals.plos.org plosone article?id=10.1371 journal.pone.0149157 , which reads: *The authors would like to correct Fig 2A and Fig 4. In Fig 2A, while preparing the figure for publication, the same image was erroneously used for the Lycop 5 u03bcM plate and the beta-carot 10u03bcM plate. The authors have provided a corrected version of Fig 2, which includes the correct image for the Lycop 5 u03bcM plate. In Fig 4, while preparing the figure for publication, the same image was erroneously used for the Lycop 5u03bcM flow cytometry plot and the beta-carot 5u03bcM plot. The authors have provided a corrected version of Fig 4, which includes the correct image for the beta-carot 5u03bcM plot. The underlying data and unedited images for Fig 2A and Fig 4 are available as Supporting Information. The authors confirm that these errors do not alter their results.* Here is the original Figure 2A: * Red boxes: the Lycop 5 uM and b-carot 10 uM panels look the same if one of the two is rotated 180 degrees. ![file] Here is the original Figure 4. * Blue boxes: The Lycop 5 uM and b-carot 5 uM panels look the same ![file] ,