Effect of ROS on parthenolide-induced apoptosis in multiple myeloma cell / 中国药理学通报

ABSTRACT

Aim To explore the effect of sesquiterpene lactone parthenolide(PL) on primary multiple myeloma(MM) cell and cell lines and its molecular mechanisms.Methods Fresh bone marrow cells from MM patients and MM cell lines KMM-1 and MM1S were used for in vitro culture study.The cell survival rate was examined by Trypan Blue exclusion.The change of nucleolus stained with DAPI was observed under fluorescent microscope.Reactive oxygen species(ROS) levels and mitochondrial membrane potential(MMP) were detected by flow cytometry.Results 2.5 ?mol?L-1 PL induced MM cell apoptosis and MMP was profoundly decreased in KMM-1 and MM1S cells.In contrast,normal lymphocytes cells were unaffected by the same conditions.KMM-1 and MM1S cells showed large increases of ROS levels 10 h after 2.5 ?mol?L-1 PL treatment.The free radical scavenger L-N-acetylcystein(L-NAC) pretreatment completely inhibited ROS generation,cell death and nuclear fragmentation by PL.Diphenylene iodonium chloride(DPI) pretreatment in a dose of 2.5 ?mol?L-1 strongly inhibited PL-mediated ROS generation,nuclear fragmentation in KMM-1 and MM1S cells.Conclusions PL strongly induces apoptosis in MM cell,while normal lymphocytes cells are completely unaffected by the same conditions.Since its proapoptotic activity appears to be mediated through induction of oxidative stress in MM cells,its possible mechanism is that NADPH oxidase activation is involved in PL-mediated ROS generation.