PUBLICATION
Preclinical Evidence of Progesterone as a New Pharmacological Strategy in Human Adrenocortical Carcinoma Cell Lines
- Authors
- Tamburello, M., Abate, A., Rossini, E., Basnet, R.M., Zizioli, D., Cosentini, D., Hantel, C., Laganà, M., Tiberio, G.A.M., Grisanti, S., Memo, M., Berruti, A., Sigala, S.
- ID
- ZDB-PUB-230414-58
- Date
- 2023
- Source
- International Journal of Molecular Sciences 24(7): (Journal)
- Registered Authors
- Keywords
- ACC cell lines, adrenocortical carcinoma, apoptosis, autophagy, invasion, metastasis, migration, progesterone, zebrafish model
- MeSH Terms
-
- Adrenocortical Carcinoma*/pathology
- Progesterone/pharmacology
- Progesterone/therapeutic use
- Matrix Metalloproteinase 2
- Animals
- Humans
- Zebrafish
- Cell Line, Tumor
- Adrenal Cortex Neoplasms*/metabolism
- PubMed
- 37047801 Full text @ Int. J. Mol. Sci.
Citation
Tamburello, M., Abate, A., Rossini, E., Basnet, R.M., Zizioli, D., Cosentini, D., Hantel, C., Laganà, M., Tiberio, G.A.M., Grisanti, S., Memo, M., Berruti, A., Sigala, S. (2023) Preclinical Evidence of Progesterone as a New Pharmacological Strategy in Human Adrenocortical Carcinoma Cell Lines. International Journal of Molecular Sciences. 24(7):.
Abstract
Background Adrenocortical cancer (ACC) is a rare malignancy with a dismal prognosis. The treatment includes mitotane and EDP chemotherapy (etoposide, doxorubicin, and cisplatin). However, new therapeutic approaches for advanced ACC are needed, particularly targeting the metastatic process. Here, we deepen the role of progesterone as a new potential drug for ACC, in line with its antitumoral effect in other cancers.
Methods NCI-H295R, MUC-1, and TVBF-7 cell lines were used and xenografted in zebrafish embryos. Migration and invasion were studied using transwell assays, and MMP2 activity was studied using zymography. Apoptosis and cell cycle were analyzed by flow cytometry.
Results Progesterone significantly reduced xenograft tumor area and metastases formation in embryos injected with metastatic lines, MUC-1 and TVBF-7. These results were confirmed in vitro, where the reduction of invasion was mediated, at least in part, by the decrease in MMP2 levels. Progesterone exerted a long-lasting effect in metastatic cells. Progesterone caused apoptosis in NCI-H295R and MUC-1, inducing changes in the cell-cycle distribution, while autophagy was predominantly activated in TVBF-7 cells.
Conclusion Our results give support to the role of progesterone in ACC. The involvement of its analog (megestrol acetate) in reducing ACC progression in ACC patients undergoing EDP-M therapy is now under investigation in the PESETA phase II clinical study.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping