The redox status of human breast cancer cell lines (MCF-7 and MDA-MB231) treated with novel dinuclear berenil-platinum(II) complexes

This study compared the effects of cisplatinum and novel berenil-platinum(II) complexes on the redox status of breast cancer cells that were estrogen receptor-positive (MCF-7) or estrogen receptor-negative (MDA-MB231). Both cell lines were treated with cisplatinum or the following berenil-platinum(II) complexes: Pt-2(isopropylamine)(4)(berenil)(2), Pt-2(piperidine)(4)(berenil)(2), Pt-2(2-picoline)(4)(berenil)(2), Pt-2(3-picoline)(4)(berenil)(2), and Pt-2(4-picoline)(4)(berenil)(2). Changes in levels of reactive oxygen species, levels and activities of antioxidants, and lipid peroxidation products levels were measured. All investigated compounds enhanced ROS generation, reduced the activity of antioxidant enzymes (e.g., glutathione peroxidase and glutathione reductase), and decreased levels of small-molecule antioxidants (GSH, vitamins E and A). Such conditions are conducive to generating oxidative stress and phospholipids peroxidation. Cellular phospholipids in MCF-7 cells were most sensitive to the Pt-2(isopropylamine)(4)(berenil)(2) complex, whereas MDA-MB231 cells were not particularly sensitive to any berenil-platinum(II) complex. These findings will facilitate future anticancer drug design strategy for breast cancer pharmacotherapy.