A novel ruthenium(ii) gallic acid complex disrupts the actin cytoskeleton and inhibits migration, invasion and adhesion of triple negative breast tumor cells

Dalton Trans. 2021 Jan 7;50(1):323-335. doi: 10.1039/d0dt03490h. Epub 2020 Dec 11.

Abstract

This work describes the synthesis of three new ruthenium(ii) complexes with gallic acid and derivatives of the general formula [Ru(L)(dppb)(bipy)]PF6, where L = gallate (GAC), benzoate (BAC), and esterified-gallate (EGA), bipy = 2,2'-bipyridine and dppb = 1,4-bis(diphenylphosphino)butane. The complexes were characterized by elemental analysis, molar conductivity, NMR, cyclic voltammetry, UV-vis and IR spectroscopy, and two of them by X-ray crystallography. Cell viability assays show promising results, indicating higher cytotoxicity of the complexes in MDA-MB-231 cells, a triple-negative breast cancer (TNBC) cell line, compared with the hormone-dependent MCF-7 cell line. Studies in vitro with the MDA-MB-231 cell line showed that only Ru(BAC) and Ru(GAC) interacted with BSA. Besides that, the Ru(GAC) complex, which has a polyphenolic acid, interacted in an apo-Tf structure and function dependent manner and it was able to inhibit the formation of reactive oxygen species. Ru(GAC) was able to cause damage to the cellular cytoskeleton leading to inhibition of some cellular processes of TNBC cells, such as invasion, migration, and adhesion.

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoproteins / metabolism
  • Biphenyl Compounds / chemistry
  • Cell Adhesion / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Gallic Acid / chemistry
  • Gallic Acid / pharmacology*
  • Humans
  • Mice
  • Picrates / chemistry
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Ruthenium / chemistry
  • Ruthenium / pharmacology*
  • Serum Albumin, Bovine / metabolism
  • Transferrin / metabolism
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Apoproteins
  • Biphenyl Compounds
  • Coordination Complexes
  • Picrates
  • Pyridines
  • Transferrin
  • apotransferrin
  • Serum Albumin, Bovine
  • Gallic Acid
  • Ruthenium
  • 1,1-diphenyl-2-picrylhydrazyl