Antiproliferative activity of two copper (II) complexes on colorectal cancer cell models: Impact on ROS production, apoptosis induction and NF-κB inhibition

RUIZ, MARIA C.; PERELMULTER, KAREN; LEVÍN, PEDRO; ROMO, ADOLFO I.B.; LEMUS, LUIS; -FOGOLÍN, MARIELA BOLLATI; LEÓN, IGNACIO E.; DI VIRGILIO, ANA LAURA

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES

ELSEVIER SCIENCE BV

Año: 2022 vol. 169

0928-0987

The main goal of this work was to screen the antiproliferative activity and mechanism of actions of two coppercomplexes: [Cu(dmp)2(CH3CN)]2+(1) and [Cu(phen)2(CH3CN)]2+(2) on 2D and 3D colorectal cancer cellsmodels. Cell viability studies on three colorectal cancer cell lines (HT-29, LS174T, Caco-2) displayed that 1showed more robust antiproliferative activity than 2 and cisplatin. Intracellular copper content (63.24% and48.06% 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. Thiseffect takes place along with the depolarization of the mitochondrial membrane at 2 µM. Besides, both complexesincreased apoptosis on three cancer cell lines at low micromolar concentrations (0.5?2.5μM). Moreover, 1 and 2inhibited NF-κB pathway both in HT-29-NF-kB-hrGFP monolayer (0.5 to 1μM) and spheroids HT-29 GFP (5 to10μM). 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 inthe monolayer and the 3D model.