N 4 -aryl substituted thiosemicarbazones derived from 1-indanones as potential anti-tumor agents for breast cancer treatment

LOAIZA PEREZ, ANDREA I.; CALLERO, MARIANA A.; LOAIZA PEREZ, ANDREA I.; CALLERO, MARIANA A.; SORAIRES SANTACRUZ, MARIA CRISTINA; FINKIELSZTEIN, LILIANA M.; SORAIRES SANTACRUZ, MARIA CRISTINA; FINKIELSZTEIN, LILIANA M.; SÓLIMO, ALDANA; BAL DE KIER JOFFÉ, ELISA; SÓLIMO, ALDANA; BAL DE KIER JOFFÉ, ELISA

JOURNAL OF CELLULAR PHYSIOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2018 vol. 233 p. 4677 - 4687

0021-9541

Breast cancer is the first cause of cancer death in women. Many patients are resistant to current therapies, and even those were sensitive at first may eventually become resistant later. Thiosemicarbazones (TSCs) are synthetic compounds that exhibit several pharmacological activities. In this study, we investigated the potential anti-tumor activity of a set of N 4 -arylsubstituted TSCs (N 4 -TSCs) on human breast cancer cell lines. Studies on the effect of N 4 -TSCs (T1, T2, and T3) were carried on MCF-7, MDA-MB 231, and BT 474 cell lines which differ in their expression of ER, PR, and Her2/neu. Non-transformed MCF-10A breast cell line were used as normal cells. Action of N 4 -TSCs were evaluated by proliferation assay, quantification of apoptosis and cell cycle analysis. Modulation of clonogenic efficiency and migratory capacity by N 4 -TSCs were also evaluated. We further investigated the effects of N 4 -TSCs on ROS level and Ribonucleotide Reductase (RR) activity. We analyzed the action of these compounds on cellular mammosphere-forming capacity. We found that T1 and T2 had specific anti-tumor effect on all breast cancer cell lines based on their pro-apoptotic action and inhibitory effect on clonogenic efficiency and cell migration capacity. We also showed that both compounds increased ROS level and inhibited RR activity. Finally, we found that all N 4 -TSCs diminished mammospehere-forming capacity of MCF-7 and BT 474 cells. N 4 -TSCs showed specific anti-tumor action on human breast cancer cells independently their biomarkers expression pattern. Our results place these compounds as promising novel anti-tumor drugs with potential therapeutic application against different types of breast cancer.