ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Evaluation of an isatin-derived ligand and its metal complexes as potential anticancer agents in breast adenocarcinoma cells

Riyam N. Khalaf, Amal I. Hassan, Zeinab A. El-Shafiey, Abeer A. Faheim, Sattar S. Ibrahim, and Hosam M. Saleh

College of Applied Sciences, University of Fallujah, Fallujah, Iraq

E-mail: riamnafiaa@uofallujah.edu.iq

Received: 8 April 2024  Accepted: 19 December 2024

Abstract:

This study investigates the anticancer potential of a novel ligand, 3-(2-mercapyo-phenylimino)-1,3-dihydro-indol-2-one, along with its metal ions, iron (Fe) and lanthanum (La), against “MDA-MB-231” breast adenocarcinoma cells in both in vitro and in vivo settings using a model of Ehrlich carcinoma in mice. In vitro cytotoxicity assays on MDA-MB-231 cells and in vivo Ehrlich carcinoma BALB/c mice model were used to assess anticancer efficacy and mechanisms. In vitro, we conducted cell viability assays to assess the cytotoxic effects of the ligand and its metal ions on MDA-MB-231 cells. Metal complexes showed potent cytotoxicity (IC50: Fe 5.745 μM, La 6.1705 μM) compared to the ligand (10 μM). Flow cytometry revealed apoptosis as the primary cell death mechanism. In vivo studies demonstrated significant tumor growth reduction, with metal complexes exhibiting superior efficacy. Biomarker analysis showed regulation of apoptosis (Caspase-3 and Caspase-9) and inflammatory (STAT3, TNF-α) pathways. Our results suggest that the novel 3-(2-mercapyo-phenylimino)-1,3-dihydro-indol-2-one-based ligand and its metal complexes, specifically iron (Fe (III)) and lanthanum (La (III)), hold promise as potential anticancer agents against breast adenocarcinoma cells in vitro and in vivo. Furthermore, the enhanced effectiveness of the metal complexes may be attributed to their regulation of apoptosis and inflammation-related biomarkers.

Keywords: 3-(2-Mercapyo-phenylimino)-1,3-dihydro-indol-2-one-based ligand; Breast adenocarcinoma; Anticancer; Apoptosis; Ligand; Necrosis; Metal complexes

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-024-03873-w

Chemical Papers 79 (3) 1539–1560 (2025)