A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells.

摘要: Piplartine (piperlongumine) is a plant-derived compound found in some Piper species that became novel potential antineoplastic agent. In the present study, we synthesized platinum complex containing piplartine derivative cis-[PtCl(PIP-OH)(PPh3)2]PF6 (where, PIP-OH = demethylated derivative; and PPh3 triphenylphosphine) with enhanced cytotoxicity different cancer cells, investigated its apoptotic action human promyelocytic leukemia HL-60 cells. The structure of ligand was characterized by X-ray crystallographic analysis resulting infrared, molar conductance measurements, elemental NMR experiments. We more potent than panel cell lines. Apoptotic morphology, increased internucleosomal DNA fragmentation, without membrane permeability, loss mitochondrial transmembrane potential, phosphatidylserine externalization caspase-3 activation were observed complex-treated Treatment also caused marked increase production reactive oxygen (ROS), pretreatment N-acetyl-L-cysteine, an antioxidant, reduced complex-induced apoptosis, indicating ROS-mediated apoptosis pathway. Important, p38 MAPK inhibitor (PD 169316) MEK (U-0126), known to inhibit ERK1/2 activation, prevented apoptosis. did not induce intercalation cell-free assays. conclusion, exhibits cells triggers ROS/ERK/p38-mediated