Clozapine, a new therapeutic approach for breast cancer?

NICOUD, M B; MARTINEL LAMAS, D J; STERLE HA; PERAZZO, JC; CREMASCHI, G A; MEDINA, V A

Mar del Plata

Congreso; LXI Reunión anual SAIC, LXIV Reunión anual SAI, XLVIII Reunión anual SAFE, VII Reunión anual NANOMEDAR, V Congreso Nacional AACYTAL; 2016

SAIC, SAI, SAFE, NANOMEDAR, AACYTAL

Previous data provide evidence supporting the anticancer effects of antipsychotics that could partially explain the lower incidence of cancer in patients with schizophrenia compared with the general population. We have previously demonstrated that clozapine inhibited proliferation of human breast cancer and melanoma cells. The aim of this work was to investigate the in vitro and in vivo antitumor activity of clozapine in 4T1 triple negative breast cancer (TNBC) model. For that purpose, the effect of clozapine on processes associated with cell death and survival, metabolism of ROS and DNA damage was studied in murine 4T1 breast cancer cells. Clozapine effects on tumor progression was further investigated in syngeneic mice, inoculated orthotopically with 4T1 murine TNBC cells.Results indicate that clozapine inhibited clonogenic proliferation and produced a 2-fold decrease in BrdU incorporation of 4T1 cells (P˂0.01). This effect was associated with an increase in the differentiation marker Nile red evaluated by flow cytometry. Accordingly, in vivo treatment of 4T1 tumors with clozapine (1 mg/kg.day) reduced tumor weight (1.3±0.1 vs. 2.1±0.3 g, P˂0.05) and volume (1.3±0.1 g vs. 1.9±0.3 cm3, P˂0.05). Histopathological studies demonstrate that tumors of the clozapine-treated group were microscopically homogeneous with extended areas of differentiation (e.g. glands).We conclude that clozapine produces antitumoral effects in vitro and in mouse syngeneic model of TNBC, suggesting that it could be a potential therapeutic agent in the treatment of breast cancer.