Ruthenium(II)–Arene Thiocarboxylates: Identification of a Stable Dimer Selectively Cytotoxic to Invasive Breast Cancer Cells

Liam J. Stephens, Aviva Levina, Iman Trinh, Victoria L. Blair, Melissa V. Werrett, Peter A. Lay, Philip C. Andrews

Research output: Contribution to journalArticleResearchpeer-review

Abstract

RuII-arene complexes provide a versatile scaffold for novel anticancer drugs. Seven new RuII-arene-thiocarboxylato dimers were synthesized and characterized. Three of the complexes (2 a, b and 5) showed promising antiproliferative activities in MDA-MB-231 (human invasive breast cancer) cells, and were further tested in a panel of fifteen cancerous and noncancerous cell lines. Complex 5 showed moderate but remarkably selective activity in MDA-MB-231 cells (IC50=39±4 μm Ru). Real-time proliferation studies showed that 5 induced apoptosis in MDA-MB-231 cells but had no effect in A549 (human lung cancer, epithelial) cells. By contrast, 2 a and b showed moderate antiproliferative activity, but no apoptosis, in either cell line. Selective cytotoxicity of 5 in aggressive, mesenchymal-like MDA-MB-231 cells over many common epithelial cancer cell lines (including noninvasive breast cancer MCF-7) makes it an attractive lead compound for the development of specifically antimetastatic Ru complexes with low systemic toxicity.

Original languageEnglish
Pages (from-to)1188-1200
Number of pages13
JournalChemBioChem
Volume21
Issue number8
DOIs
Publication statusPublished - 17 Apr 2020

Keywords

  • anticancer agents
  • antimetastatic
  • apoptosis
  • breast cancer
  • ruthenium

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