title: Cytotoxic activity of gemcitabine, alone or in combination with mitotane, in adrenocortical carcinoma cell lines.
abstract: We aimed at investigating in vitro the cytotoxic activity (determined using WST-1, apoptosis and cell cycle assays) of gemcitabine, alone or in combination with mitotane, in mitotane-sensitive H295R and mitotane-insensitive SW-13 cells. Results of these experiments were compared with drug-induced modulation of RRM1 gene, the specific target of gemcitabine. In H295R cells, mitotane and gemcitabine combinations showed antagonistic effects and interfered with the gemcitabine-mediated inhibition of the S phase of the cell cycle. By contrast, in SW-13 cells, except when mitotane was sequentially administered prior to gemcitabine, the combination of the two drugs was synergistic. Such opposite effects were associated with opposite expression profiles of the target gene, with significant up-modulation in H295R but not in SW-13 under gemcitabine and mitotane combination treatment.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, 10043 Orbassano, Turin, Italy. Electronic address: antonina.germano@unito.it.
authors.forename: Antonina
authors.initials: A
authors.lastname: Germano
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, 10043 Orbassano, Turin, Italy. Electronic address: ida.rapa@unito.it.
authors.forename: Ida
authors.initials: I
authors.lastname: Rapa
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, 10043 Orbassano, Turin, Italy. Electronic address: marco.volante@unito.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.affiliation: Department of Medical Sciences, University of Turin, 10126 Turin, Italy. Electronic address: nicola.lobuono@unito.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Lo Buono
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, 10043 Orbassano, Turin, Italy. Electronic address: sonia.carturan@unito.it.
authors.forename: Sonia
authors.initials: S
authors.lastname: Carturan
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, 10043 Orbassano, Turin, Italy. Electronic address: alfredo.berruti@gmail.com.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, 10043 Orbassano, Turin, Italy. Electronic address: massimo.terzolo@unito.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Terzolo
authors.affiliation: Department of Oncology, University of Turin, San Luigi Hospital, 10043 Orbassano, Turin, Italy. Electronic address: mauro.papotti@unito.it.
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008939:Mitotane / Q000494:pharmacology / Q000627:therapeutic use*; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D008939:Mitotane; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D000093542:Gemcitabine
keywords: Adrenocortical cancer; Cell lines; Gemcitabine; Mitotane