Anti-metastatic action of an N4-aryl substituted thiosemicarbazone on advanced triple negative breast cancer.

SORAIRES SANTACRUZ, M.C.; BAL DE KIER JOFFÉ, E.; SÓLIMO, A.M.; COGGIOLA, O.; CALLERO, M.A.; VANZULLI, S.; FINKIELSZTEIN, L.; SORAIRES SANTACRUZ, M.C.; BAL DE KIER JOFFÉ, E.; SÓLIMO, A.M.; COGGIOLA, O.; CALLERO, M.A.; VANZULLI, S.; FINKIELSZTEIN, L.

Heliyon

CelPress

Año: 2020 vol. 6 p. 1 - 11

2405-8440

Purpose:Advanced triple negative breast cancer (ATNBC) is defined by a lack of expression of hormones receptorsas well as HER2/neu and its high probability of visceral metastasis. This pathology is associated with a poorprognosis. Previously, we found that T2, anN4-arylsubstituted thiosemicarbazone (N4-TSC), had cytotoxic effecton human breast cancer cells lines. Hence, in this study, we investigated the anti-metastasic action of T2 onATNBC.Methods:In order to deepen T2 action mode on ATNBC, wefirst confirmed T2 cytotoxicity on a panel of TNBCcells and then continued studying T2 effectsin vitroanin vivoon the syngeneic 4T1 mouse model.Results:We found that T2 had a cytotoxic effect comparable to chemotherapeutics used in present treatmentschemes for ATNBC. T2 treatment not only induced apoptosis, but it also down-modulated 4T1 invasive andmetastatic-associated capacities, such as clonogenicity, migration and metallo-proteases activity. Moreover, thisagent reduced the number of 4T1 cancer stem cells. Finally, T2 treatment induced a more differentiated cellphenotype and the overexpression of the metastasis suppressor gene NDRG-1.In vivoassays showed that T2reduced tumor burden, down modulated local tumor invasion and significantly reduced the number of lungmetastases in the 4T1 advanced TNBC murine model, while the compound did not exhibit intolerable toxicity.Conclusion:This study provided evidence that T2 not only exerted an anti-tumor activity but it also showed anti-invasive and anti-metastatic actions on ATNBCin vivoandin vitro, suggesting that T2 could be considered as apromising therapy that deserves further analysis.