Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 356, Issue -, Pages 127-138Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2018.08.004
Keywords
Copper(II) Complexes; DNA Damage; Cell Cycle; Apoptosis; Antitumor Activity; Breast Cancer
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Copper (II) complexes are promising in the development of new synthetic models for cancer treatment. In this context, we synthesized a new copper complex containing the pharmacophore group 1,4-dioxo-2-butenyl, the Bis (((Z7-4-((4-chlorophenyl) amino)-4-oxobut-2-enoyl)oxy) copper compound and we evaluated its antitumor activity in 4 T1 murine mammary adenocarcinoma cells and their toxicogenic effect in Swiss mice. The compound demonstrated cytotoxicity and genotoxicity to 4 T1 cells, and after cell cycle arrest in G1, which occurred by the increase in ATM and p21 expression, it induced the cells to apoptosis by increasing BAX and caspase-7. In vivo the compound was genotoxic in mice but did not show permanent damage, observed by the absence of increased micronucleus frequency, and did not induce changes in the biometric parameters of the animals. These results indicate that the new copper complex, described firstly in this work, presents therapeutic potential for breast cancer.
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