Effect of ruthenium(II) complexes on MDA-MB-231 cells and lifespan/tumor growth in gld-1mutant, Daf-16 TF and stress productive genes: A perspective study.

Nandhini, S; Thiruppathi, G; Ranjani, M; Puschmann, H; Ravi, M; Sundararaj, P; Prabhakaran, R

Abstract

Pincer type coumarin based N-substituted semicarbazone ligands HL and their corresponding ruthenium(II) complexes (1-4) were synthesized, analyzed and confirmed by various spectro analytical techniques. The molecular structure of the ligand HL and complex 3 was confirmed by single crystal X-ray diffraction analysis. The stoichiometry of complexes 1, 2 and 4 was confirmed by high resolution mass spectroscopy (HRMS). The binding affinity of the compounds with CT-DNA (Calf Thymus DNA) and BSA (Bovine Serum Albumin) was established by absorption and emission titration methods. The results of In vitro cytotoxicity showed the significant cytotoxic potential of the complexes against MDA-MB-231 cells (TNBC- Triple-negative breast cancer). Among the complexes, 1 and 4 have shown appreciable results. Further, antimigratory activity against the MDA-MB-231 cells was studied for the complexes 1 and 4. The percentage cell cycle arrest, apoptosis and necrosis were explored by flow cytometry. The in vivo anti-tumor activity of the complexes 1 and 4 using C. elegans as model organism was established by using the tumoral C. elegans strain JK1466 (gld-1(q485)), which bears a mutation in the gld-1 tumor suppressor gene. We have determined the effect of our complexes on tumor gonad reduction and found to be non toxic to the JK1466 worms and they have prolonged their mean lifespan with potential antioxidant ability by overcoming stress responses. Overall, our study reported herein demonstrated that the complexes 1 and 4 could be established as potential metallo-drugs substantiating further exploration. [Abstract copyright: Copyright © 2024 Elsevier Inc. All rights reserved.]

Citation

Nandhini, S., Thiruppathi, G., Ranjani, M., Puschmann, H., Ravi, M., Sundararaj, P., & Prabhakaran, R. (2024). Effect of ruthenium(II) complexes on MDA-MB-231 cells and lifespan/tumor growth in gld-1mutant, Daf-16 TF and stress productive genes: A perspective study. Journal of Inorganic Biochemistry, 257, Article 112580. https://doi.org/10.1016/j.jinorgbio.2024.112580

• Journal Article Type: Article
• Acceptance Date: Apr 26, 2024
• Online Publication Date: Apr 28, 2024
• Publication Date: Apr 28, 2024
• Deposit Date: May 22, 2024
• Journal: Journal of Inorganic Biochemistry
• Print ISSN: 0162-0134
• Electronic ISSN: 1873-3344
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 257
• Article Number: 112580
• DOI: https://doi.org/10.1016/j.jinorgbio.2024.112580
• Keywords: Ruthenium(II) complexes, MTT assay, DNA/protein binding, C. elegans, FACS
• Public URL: https://durham-repository.worktribe.com/output/2450748