Etoposide is a plant alkaloid which acts as an inhibitor of topoisomerase II (IC50 = 60.3 μM). Notably, this compound can have much greater potencies when evaluated in cell-based cytotoxicity assays (e.g., IC50 = 5.14 nM for MCF-7 cells). Etoposide inhibits DNA synthesis by forming a ternary complex with DNA and topoisomerase II, inducing breaks in double stranded DNA. Accumulated breaks in DNA prevent entry into mitosis and lead to cell death. Recent bioassay data suggest that etoposide can also inhibit nuclear receptor coactivator 3 (IC50 = 2.48 μM), a steroid receptor coactivator with histone acetyltransferase activity. Interestingly, histone deacetylase inhibitors can sensitize multidrug-resistant cancer cells to etoposide.