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Anticancer activity of two novel ruthenium compounds in gastric cancer cells

Author:
Ramírez-Rivera, S., Pizarro, S., Gallardo, M., Gajardo, F., Delgadillo, A., De La Fuente-Ortega, E., MacDonnell, F.M., Bernal, G.
Source:
Life sciences 2018 v.213 pp. 57-65
ISSN:
0024-3205
Subject:
antineoplastic activity, apoptosis, caspases, cisplatin, confocal microscopy, cytotoxicity, enzyme activity, gene overexpression, genes, humans, neoplasm cells, quantitative polymerase chain reaction, reverse transcriptase polymerase chain reaction, ruthenium, stomach neoplasms
Abstract:
Ruthenium (II) complexes are promising anticancer molecules due its pharmacological properties and selectivity to cells tumor. The aim of this work was to study the cytotoxic activity, and apoptosis induction of two new ruthenium complexes on a human gastric cancer cell line.Two ruthenium(II) complexes were synthesized: [(H2pbbzim)Ru(tpy-Ph-COOCH3)](Cl)2 (Ru-UCN1), and [(tpy)Ru(tpy-Ph-bzH)](Cl)2 (Ru-UCN3), and their anticancer capacity determined by cytotoxic assays, gene expression analysis, caspase activation and confocal microscopy.Ru-UCN3 is more notably cytotoxic than cisplatin in human gastric cancer cells AGS at 24 h, while Ru-UCN1 is more active against gastric cancer cells than cisplatin at 48 h. The complexes induce apoptosis as shown by RT-qPCR, protease activity, and confocal microscopy. Ru-UCN1 induces the overexpression of pro-apoptotic genes at 3 and 6 h, whereas Ru-UCN3 induces overexpression of these genes at 12 and 24 h. Ru-UCN1 treatment shows a strong activation of caspases 3/7 at 24 h, which was not observed for Ru-UCN3 treatment in the same timeframe.Taken together, this data suggests that Ru-UCN1 and to a lesser extent, Ru-UCN3, may be interesting anticancer agents for gastric cancer.
Agid:
6176087