Evaluation of biomolecular interactions and in vitro cytotoxic activity of mononuclear and polymeric copper(ii)-based complexes against triple-negative breast cancer cells

Abstract

Herein, we report the syntheses, characterizations and anticancer activities of two Cu(II) complexes (C1 and CP1) as chemotherapeutic agents. The compounds were synthesized under different conditions, and interestingly, complex C1 was mononuclear and CP1 was polymeric. The molecular structures of C1 and CP1 were validated by various spectral techniques, viz., electronic spectroscopy, FT-IR, EPR, sc-XRD and other analytical techniques. Single crystal X-ray crystallographic studies of C1 revealed a triclinic system with the P space group, while CP1 revealed an orthorhombic crystal system with the space group pbca. In vitro DNA binding studies were carried out to investigate their chemotherapeutic potential, and the combined results revealed an electrostatic mode of interaction. The cytotoxicity of the synthesized compounds was examined against two triple-negative breast cancer (TNBC) cells of different morphologies, viz., MDA-MB-468 and MDA-MB-231. Results showed that CP1 exhibited better anticancer efficacy and induced apoptosis in TNBC cells. In order to validate the apoptosis-mediated cell death, western blot assays were also carried out, which revealed a significant reduction in the levels of apoptosis-related proteins, especially Bcl-2 and Pro-caspase, in the presence of CP1 treatment. Furthermore, the results of immunoblotting assays corroborated well with flow cytometry analysis, which indicated early or late apoptosis.