Cytotoxic effect of trabectedin in human adrenocortical carcinoma cell lines and primary cells

Andrea Abate, Elisa Rossini, Sara Anna Bonini, Martina Fragni, Deborah Cosentini, Guido Albero Massimo Tiberio, Diego Benetti, Constanze Hantel, Marta Laganà, Salvatore Grisanti, Massimo Terzolo, Maurizio Memo, Alfredo Berruti, Sandra Sigala*

*Corresponding author for this work
2 Citations (Scopus)


Mitotane is the only drug approved for the treatment of adrenocortical carcinoma (ACC). The regimen to be added to mitotane is a chemotherapy including etoposide, doxorubicin, and cisplatin. This pharmacological approach, however, has a limited efficacy and significant toxicity. Evidence indicates that ACC seems to be sensitive to alkylating agents. Trabectedin is an anti-tumor drug that acts as an alkylating agent with a complex mechanism of action. Here, we investigated whether trabectedin could exert a cytotoxic activity in in vitro cell models of ACC. Cell viability was evaluated by MTT assay on ACC cell lines and primary cell cultures. The gene expression was evaluated by q-RT-PCR, while protein expression and localization were studied by Western blot and immunocytochemistry. Combination experiments were performed to evaluate their interaction on ACC cell line viability. Trabectedin demonstrated high cytotoxicity at sub-nanomolar concentrations in ACC cell lines and patient-derived primary cell cultures. The drug was able to reduce /β catenin nuclear localization, although it is unclear whether this effect is involved in the observed cytotoxicity. Trabectedin/mitotane combination exerted a synergic cytotoxic effect in NCI-H295R cells. Trabectedin has antineoplastic activity in ACC cells. The synergistic cytotoxic activity of trabectedin with mitotane provides the rationale for testing this combination in a clinical study.

Original languageEnglish
Article number928
Issue number4
Publication statusPublished - 04.2020


Dive into the research topics of 'Cytotoxic effect of trabectedin in human adrenocortical carcinoma cell lines and primary cells'. Together they form a unique fingerprint.

Cite this