Anticancer activity and mechanism of action evaluation of an acylhydrazone Cu(II) complex toward breast cancer cells, spheroids and mammospheres.

BALSA, LUCIA M.; RODRIGUEZ, MARIA R.; PARAJÓN-COSTA, BEATRIZ S.; GONZÁLEZ BARÓ, ANA C.; LAVECCHIA, MARTIN J.; LEÓN, IGNACIO

CHEMMEDCHEM

WILEY-V C H VERLAG GMBH

Año: 2022

1860-7179

Abstract: The purpose of this work was to screen the anticancer activity and mechanisms of action of Cu(II)-acylhydrazone complex [Cu(HL)(H2O)](NO3)∙H2O, (CuHL), to find a potential novel agent for breast chemotherapies. Cytotoxicity studies on MCF7 demonstrated that CuHL showed stronger anticancer properties than cisplatin over breast cancer cell models. Computational simulations showed that CuHL could interact in the minor groove of the DNA dodecamer, inducing a significant genotoxic effect on both cancer cells from 0.5 to 1 µM. In this sense, molecular docking and molecular dynamics simulations showed that compound could interacts with 20S proteasome subunits. Also, cell proteasome experiments using breast cancer cells revealed that the complex inhibited the proteasomal activity. Moreover, CuHL induced apoptosis on breast cancer cells at very low micromolar concentrations (0.5-2.5 µM) and displayed relevant anticancer activity over spheroids derived from MCF7. Ultimately, CuHL diminished the number of mammospheres formed disturbing their morphology and size.