Related Experiment Video
Updated: May 11, 2026
![Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60445.jpg&w=3840&q=50)
Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
Published on: December 19, 2019
Lycopene and beta-carotene induce growth inhibition and proapoptotic effects on ACTH-secreting pituitary adenoma
Natália F Haddad1, Anderson J Teodoro, Felipe Leite de Oliveira
1Instituto 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.
Insights
Beta-carotene and lycopene, found in functional foods, reduce pituitary adenoma cell viability and ACTH secretion. These carotenoids may offer a new treatment for Cushing
Area of Science:
- Endocrinology
- Cell Biology
- Nutritional Science
Background:
- Pituitary adenomas cause significant morbidity due to hormonal imbalances and tumor compression.
- Carotenoids, found in functional foods, are known for their potential to mitigate chronic diseases.
- Understanding carotenoid effects on pituitary adenoma cells is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the impact of beta-carotene and lycopene on ACTH-secreting pituitary adenoma cells (AtT20).
- To assess the effects on cell viability, proliferation, cell cycle, apoptosis, and hormone secretion.
- To explore the influence on intercellular communication and specific protein expression (connexin 43, Skp2, p27(kip1)).
Main Methods:
- AtT20 cells were treated with varying concentrations of beta-carotene and lycopene for 48 and 96 hours.
- Assays included cell viability, colony formation, cell cycle analysis, apoptosis detection, and ACTH secretion measurement.
- Intercellular communication, connexin 43 phosphorylation, and expression of Skp2 and p27(kip1) were evaluated.
Main Results:
- Both beta-carotene and lycopene decreased AtT20 cell viability and colony formation.
- Carotenoids induced apoptosis and altered cell cycle progression in a dose-dependent manner.
- ACTH secretion was reduced, intercellular communication was inhibited, and connexin 43 phosphorylation increased, alongside changes in Skp2 and p27(kip1) expression.
Conclusions:
- Lycopene and beta-carotene demonstrate potential in negatively modulating the malignant phenotype of pituitary adenoma cells.
- The observed effects may involve alterations in connexin 43, Skp2, and p27(kip1) expression.
- These carotenoids suggest a potential novel pharmacological approach for treating Cushing's disease.
Related Concept Videos
Abnormal Proliferation
Mutagenicity and Carcinogenicity
Inhibition of Cdk Activity
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
GPCRs Regulate Adenylyl Cylase Activity
Two...
Mitogens and the Cell Cycle
