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

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.

Fucoxanthin increases lifespan of Drosophila melanogaster and Caenorhabditis elegans

“…For example, lycopene was shown increasing the quality of sperm in males by protecting them from oxidative DNA damage [3,4]. Furthermore, carotenoids demonstrate antimutagenic, anti-inflammatory and antitumor properties, helping to fight obesity and diabetes, cardiovascular diseases, osteoporosis and to stimulate tissue healing [5][6][7]. Interestingly, that β-carotene can decrease photosuppresion of human immune system [8].…”

Cytotoxic Potential of Antioxidants from Tomatoes on Tumoral Cells

“…Moreover, breast cancer (Gloria et al, 2014) as well as pituitary adenoma (Haddad et al, 2013) were negatively influenced by tomato-extracted lycopene.…”

Phytochemical, Free Radical Scavenging and Cytotoxic Assay of Cucumis Melo L. Extract and β-Carotene

“…Consumption of carotenoids is associated with reduced risk of chronic diseases, including cancer and vascular diseases [33]. β-carotene is associated with reduction in the risk of prostate cancer [34], HT-29 colon adenocarcinoma cancer cells [33] and AtT-20 mouse corticotroph tumor cell line [35]. β-carotene induced an increase of the cells in S and G2/M phases.…”

“…β-carotene induced an increase of the cells in S and G2/M phases. β-carotene induced apoptosis, reduced expression of phosphorylated-Cx43 [35]. Carotenoids inhibited AtT-20 cell proliferation and colony formation, induced apoptosis and cell cycle arrest, and reduced adrenocorticotropic hormone (ACTH) secretion [36].…”