Investigation of the Effects and Mechanisms of Anticancer Action of a Ru(II)‐Arene Iminophosphorane Compound in Triple Negative Breast Cancer Cells. (24th August 2021)

• Record Type: Journal Article
• Authors: Nayeem, Nazia; Yeasmin, Arefa; Cobos, Samantha N.; Younes, Ali; Hubbard, Karen; Contel, Maria
• Is Part Of: ChemMedChem. Volume 16:Number 21(2021)
• Page Start: 3280
• Page End: 3292
• Publication Date: 2021-08-24
• Subjects: Ruthenium -- Triple Negative Breast Cancer -- Health Disparities -- Antimetastatic -- Antiangiogenic; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202100325
• Languages: English
• ISSNs: 1860-7179

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 IC50 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. Abstract : The first preclinical attempt to assess health disparities in triple negative breast cancer treatment by using an organometallic compound (Ru‐IM) is reported. Its evaluation in TNBC cell lines derived from patients of European (MDA‐MB‐231) and African (HCC‐1806) descent affords a similar profile, displaying high cytotoxicity, apoptotic behavior and potential antimetastatic and antiangiogenic properties, plausibly involving the PI3/AKT pathway.