The molecular mechanisms and gene expression profiling for shikonin-induced apoptotic and necroptotic cell death in U937 cells

作者: Jin-Lan Piao , Zheng-Guo Cui , Yukihiro Furusawa , Kanwal Ahmed , Mati Ur Rehman

DOI: 10.1016/J.CBI.2013.06.011

关键词:

摘要: Shikonin (SHK), a natural naphthoquinone derived from the Chinese medical herb Lithospermum erythrorhizon, induces both apoptosis and necroptosis in several cancer cell lines. However, detailed molecular mechanisms involved initiation of death are still unclear. In present study, caspase-dependent was induced by SHK treatment at 1μM after 6h U937 cells, with increase DNA fragmentation, generation intracellular reactive oxygen species (ROS), fraction cells low mitochondrial membrane potential (MMP), expression BH3 only proteins Noxa tBid. Interestingly, caspase-independent also detected 10μM, observed as SYTOX® Green staining release lactate dehydrogenase (LDH). Necrostatin-1 (Nec-1) completely inhibited SHK-induced leakage LDH staining. Cell permeable exogenous glutathione (GSH) converted 10μM to apoptosis. Gene profiling revealed that 353 genes were found be significantly regulated 85 treatment, respectively. Among these genes, transcription factor 3 (ATF3) DNA-damage-inducible transcript (DDIT3) highly expressed while tumor necrosis (TNF) mainly increased treatment. These findings provide novel information for mechanism necroptosis.

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