In vitro antitumor activity of progesterone in human adrenocortical carcinoma.
Adrenal Cortex Neoplasms
/ drug therapy
Adrenocortical Carcinoma
/ drug therapy
Antineoplastic Agents, Hormonal
/ therapeutic use
Apoptosis
/ drug effects
Cell Cycle
/ drug effects
Cell Line, Tumor
Drug Screening Assays, Antitumor
Drug Synergism
Humans
Membrane Proteins
/ metabolism
Mitotane
/ therapeutic use
Primary Cell Culture
Progesterone
/ pharmacology
Progestins
/ pharmacology
Receptors, Progesterone
/ metabolism
beta Catenin
/ metabolism
Adrenocortical carcinoma
Cell viability
Progesterone
Progesterone receptor
Journal
Endocrine
ISSN: 1559-0100
Titre abrégé: Endocrine
Pays: United States
ID NLM: 9434444
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
02
07
2018
accepted:
15
10
2018
pubmed:
28
10
2018
medline:
28
4
2020
entrez:
28
10
2018
Statut:
ppublish
Résumé
The management of patients with adrenocortical carcinoma (ACC) is challenging. As mitotane and chemotherapy show limited efficacy, there is an urgent need to develop therapeutic approaches. The aim of this study was to investigate the antitumor activity of progesterone and explore the molecular mechanisms underlying its cytotoxic effects in the NCI-H295R cell line and primary cell cultures derived from ACC patients. Cell viability, cell cycle, and apoptosis were analyzed in untreated and progesterone-treated ACC cells. The ability of progesterone to affect the Wnt/β-catenin pathway in NCI-H295R cells was investigated by immunofluorescence. Progesterone and mitotane combination experiments were also performed to evaluate their interaction on NCI-H295R cell viability. We demonstrated that progesterone exerted a concentration-dependent inhibition of ACC cell viability. Apoptosis was the main mechanism, as demonstrated by a significant increase of apoptosis and cleaved-Caspase-3 levels. Reduction of β-catenin nuclear translocation may contribute to the progesterone cytotoxic effect. The progesterone antineoplastic activity was synergically increased when mitotane was added to the cell culture medium. Our results show that progesterone has antineoplastic activity in ACC cells. The synergistic cytotoxic activity of progesterone with mitotane provides the rationale for testing this combination in a clinical study.
Identifiants
pubmed: 30367443
doi: 10.1007/s12020-018-1795-x
pii: 10.1007/s12020-018-1795-x
doi:
Substances chimiques
Antineoplastic Agents, Hormonal
0
Membrane Proteins
0
PGRMC1 protein, human
0
Progestins
0
Receptors, Progesterone
0
beta Catenin
0
Progesterone
4G7DS2Q64Y
Mitotane
78E4J5IB5J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
592-601Subventions
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG17678
Pays : International
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG14411
Pays : International
Organisme : Fondazione Camillo Golgi
ID : not applicable
Pays : International
Organisme : Private Donations
ID : not applicable
Pays : International
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