In vitro cytotoxicity of cabazitaxel in adrenocortical carcinoma cell lines and human adrenocortical carcinoma primary cell cultures

Adrenocortical cancer (ACC) is a rare and aggressive malignancy with a poor prognosis. The overall 5-year survival rate of patients with ENS@T stage IV ACC is less than 15%. Systemic antineoplastic therapies have a limited efficacy and new drugs are urgently needed. Human ACC primary cultures and ce...

Full description

Saved in:
Bibliographic Details
Published in:Molecular and cellular endocrinology 2019-12, Vol.498, p.110585-110585, Article 110585
Main Authors: Fragni, Martina, Palma Lopez, Lilian Patricia, Rossini, Elisa, Abate, Andrea, Cosentini, Deborah, Salvi, Valentina, Vezzoli, Sara, Poliani, Pietro Luigi, Bosisio, Daniela, Hantel, Constanze, Tiberio, Guido A.M., Grisanti, Salvatore, Memo, Maurizio, Terzolo, Massimo, Berruti, Alfredo, Sigala, Sandra
Format: Article
Language:English
Subjects:
Adrenocortical carcinoma
Apoptosis
Cabazitaxel
Multi drug resistance
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Adrenocortical cancer (ACC) is a rare and aggressive malignancy with a poor prognosis. The overall 5-year survival rate of patients with ENS@T stage IV ACC is less than 15%. Systemic antineoplastic therapies have a limited efficacy and new drugs are urgently needed. Human ACC primary cultures and cell lines were used to assess the cytotoxic effect of cabazitaxel, and the role of P-glycoprotein in mediating this effect. Cabazitaxel reduced ACC cell viability, both in ACC cell lines and in ACC primary cell cultures. Molecular and pharmacological targeting of ABCB1/P-gp did not modify its cytotoxic effect in NCI–H295R cells, while it increased the paclitaxel-induced toxicity. Cabazitaxel modified the expression of proteins involved in cellular physiology, such as apoptosis and cell cycle regulation. The drug combination cabazitaxel/mitotane exerted an additive/moderate synergism in different ACC cell experimental models. These results provide a rationale for testing cabazitaxel in a clinical study. •Cabazitaxel was cytotoxic in ACC primary cell cultures and in ACC cell lines.•Cabazitaxel effect was insensitive to P-gp expression.•Combination treatment of cabazitaxel and mitotane exerted a synergic cytotoxicity.•Cabazitaxel activated both the extrinsic and intrinsic apoptosis in NCI–H295R cells.
ISSN:0303-7207
1872-8057
DOI:10.1016/j.mce.2019.110585