Preclinical Evaluation of a Potential Ruthenium-Based Chemotherapeutic Agent for the Treatment of Triple Negative Breast Cancer
Nazia Nayeem1,2,3, Rachele Rameau1,4, Karen Hubbard1,4, Maria Contel1,2,3
1CUNY Graduate Center – Biology PhD program,
2CUNY Brooklyn College Cancer Center
3CUNY Brooklyn College Chemistry Department
4CUNY City College Biology Department
Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer defined by the absence of expression of progesterone, estrogen, and human epidermal growth factor 2 receptors, with a higher incidence rate in pre-menopausal and women of African ancestry. Due to the inability to target a receptor, treatment is limited to nonspecific chemotherapy. A potential ruthenium-based chemotherapeutic agent has been developed, with preclinical evaluation of this complex showing significant anti-angiogenic, anti-invasive, and anti-migratory properties, along with subcellular accumulation in the mitochondria, increased ROS generation, and an apoptotic mechanism of cell death in both European and African-derived TNBC cell lines in vitro. Proteomic and epigenetic analysis has implicated the inhibition of PI3K/Akt pathway as a potential target of this drug, and a future in vivo study will be completed for the purposes of enhanced pharmacokinetic and molecular analysis from an initial study that showed 56% tumor shrinkage in TNBC MDA-MB-231cell line xenograft.
