Investigation of the Effects and Mechanisms of Anticancer Action of a Ru(II)‐Arene Iminophosphorane Compound in Triple Negative Breast Cancer Cells
Nazia Nayeem, Arefa Yeasmin, Samantha N. Cobos, Ali Younes, Karen Hubbard, Marı́a Contel
Abstract
Abstract Triple negative breast cancer (TNBC) is one of the breast cancers with poorer prognosis and survival rates. TNBC has a disproportionally high incidence and mortality in women of African descent. We report on the evaluation of Ru‐IM ( 1 ), a water‐soluble organometallic ruthenium compound, in TNBC cell lines derived from patients of European (MDA‐MB‐231) and African (HCC‐1806) ancestry (including IC 50 values, cellular and organelle uptake, cell death pathways, cell cycle, effects on migration, invasion, and angiogenesis, a preliminary proteomic analysis, and an NCI 60 cell‐line panel screen). 1 was previously found highly efficacious in MDA‐MB‐231 cells and xenografts, with little systemic toxicity and preferential accumulation in the tumor. We observe a similar profile for this compound in the two cell lines studied, which includes high cytotoxicity, apoptotic behavior and potential antimetastatic and antiangiogenic properties. Cytokine M‐CSF, involved in the PI3/AKT pathway, shows protein expression inhibition with exposure to 1 . We also demonstrate a p53 independent mechanism of action.