Anticancer Activity and Mechanism of Action Evaluation of an Acylhydrazone Cu(II) Complex toward Breast Cancer Cells, Spheroids, and Mammospheres

Abstract

The purpose of this work was to screen the anticancer activity and mechanisms of action of Cu(II)-acylhydrazone complex [Cu(HL)(H 2 O)](NO 3 )•H 2 O, (CuHL), to find a potential novel agent for breast chemotherapies. Cytotoxicity studies on MCF7 cells demonstrated that CuHL has 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 the compound could interact with 20S proteasome subunits. Also, cell proteasome experiments using breast cancer cells revealed that the complex can inhibit proteasomal activity. Moreover, CuHL induced apoptosis in breast cancer cells at very low micromolar concentrations (0.5-2.5 μM) and displayed relevant anticancer activity over spheroids derived from MCF7 cells. Ultimately, CuHL diminished the number of mammospheres formed, disturbing their morphology and size.

Anticancer and Antioxidant Activity of Water-Soluble Polysaccharides from Ganoderma aff. australe against Human Osteosarcoma Cells

“…The effect of GACP on cell proliferation was determined according to the method described by Balsa et al, with some modifications [ 85 ]. MG-63 human osteosarcoma cells were grown in a 24-well plate.…”

Cellular and molecular basis of therapeutic approaches to breast cancer

“…Many of these processes are usually dysregulated in malignant cells, and the breakdown of such important cell regulatory mechanisms frequently results in the cell's features and phenotype [23]. Similarly, the DNA of a malignant cell can be disturbed to the degree where the cells cease to exist while not affecting the replication processes [24], as will be detailed further below.…”

“…This pathway also includes the CDK inhibitor p16 protein, which inhibits the kinases responsible for phosphorylation to an active state and hence limits proliferation. The antiproliferative activity of p16 has been experimentally demonstrated in cells with functioning pRb by introducing complementary DNA (cDNA) carrying p16 using the Adp16 adenoviral vector [24]. Cancer cells expressing mutant p16 (or no p16) but wild-type pRb were 7 to 22 times more sensitive to the cytotoxic effects of Adp16 than control cells.…”

Finding New Molecular Targets of Two Copper(II)-Hydrazone Complexes on Triple-Negative Breast Cancer Cells Using Mass-Spectrometry-Based Quantitative Proteomics

“…We have previously reported the synthesis, physicochemical characterization, and antitumoral activity of two copper(II)-hydrazone complexes, [Cu(HL1)(H 2 O)](NO 3 ).H 2 O and [Cu(HL2)(H 2 O) 2 ](NO 3 ), or CuHL1 [ 21 , 22 ] and CuHL2 [ 23 ] for simplicity. In vitro studies revealed a promising anticancer activity of both complexes against breast cancer cell lines, including the TNBC line MDA-MB-231.…”