Abstract |
The main goal of this work was to screen the antiproliferative activity and mechanism of actions of two copper complexes: [ Cu(dmp)2(CH3CN)]2+ (1) and [ Cu(phen)2(CH3CN)]2+ (2) on 2D and 3D colorectal cancer cells models. Cell viability studies on three colorectal cancer cell lines (HT-29, LS174T, Caco-2) displayed that 1 showed more robust antiproliferative activity than 2 and cisplatin. Intracellular copper content (63.24% and 48.06% for 1 and 2, respectively) can explain the differences in the cytotoxicity assay. ROS production is the primary mechanism of action involved in the antiproliferative activity of 1 showing 4-, 70- and 2.5- fold increased values of ROS level for HT-29, LS174T, Caco-2 cancer cell lines, respectively. This effect takes place along with the depolarization of the mitochondrial membrane at 2 µM. Besides, both complexes increased apoptosis on three cancer cell lines at low micromolar concentrations (0.5-2.5 μM). Moreover, 1 and 2 inhibited NF-κB pathway both in HT-29-NF-kB-hrGFP monolayer (0.5 to 1 μM) and spheroids HT-29 GFP (5 to 10 μM). This inhibitory effect leads to an inactivation of the MMP-9 expression on HT-29 cell line. Altogether, these results showed that 1 exhibits antiproliferative activity on human colorectal cancer cells in the monolayer and the 3D model.
|
Authors | Maria C Ruiz, Karen Perelmulter, Pedro Levín, Adolfo I B Romo, Luis Lemus, Mariela Bollati -Fogolín, Ignacio E León, Ana Laura Di Virgilio |
Journal | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
(Eur J Pharm Sci)
Vol. 169
Pg. 106092
(Feb 01 2022)
ISSN: 1879-0720 [Electronic] Netherlands |
PMID | 34879254
(Publication Type: Journal Article)
|
Copyright | Copyright © 2021. Published by Elsevier B.V. |
Chemical References |
- NF-kappa B
- Reactive Oxygen Species
- Copper
|
Topics |
- Apoptosis
- Caco-2 Cells
- Colorectal Neoplasms
(drug therapy)
- Copper
- Humans
- NF-kappa B
- Reactive Oxygen Species
|