tretinoin and artenimol

To investigate the effect of a water-soluble novel dihydroartemisinin dimer containing nitrogen atoms SM 1044 on the apoptosis of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) NB4-R1 cells and its potential mechanism.. The effects of SM 1044 on cell apoptosis, mitochondrial transmembrane potential, and the level of reactive oxygen species (ROS) were assessed by flow cytometry. Expressions of apoptosis-related proteins were determined by Western blot. The effects of SM 1044 on MAPK (ERK, JNK) signaling pathway, PML/RARα fusion protein, and expressions of apoptosis-related proteins were detected by Western blot.. SM 1044 could significantly induce apoptosis and the loss of mitochondrial transmembrane potential in NB4-R1 cells, and activate apoptosis-related proteins caspase-3, caspase-8, caspase-9 and poly (ADP-ribose) polymerase (PARP). SM 1044 could also induce NB4-R1 cells to produce ROS. Western blot showed that SM 1044 activated the phosphorylation of MAPK (ERK, JNK) signaling pathway and down-regulated the expression of PML/RARα fusion protein.. SM 1044 can induce apoptosis of ATRA resistant APL NB4-R1 cells, which may be related to ROS/ERK and ROS/JNK signaling pathway, and can also induce by down-regulating PML/RARα fusion protein.. 新型含氮双氢青蒿素二聚体对人白血病细胞株NB4-R1细胞凋亡的影响.. 探讨新型水溶性含氮双氢青蒿素二聚体SM 1044对全反式维甲酸耐药急性早幼粒细胞白血病细胞株NB4-R1细胞凋亡的影响及其可能的机制。.. 流式细胞术检测SM 1044对细胞凋亡、线粒体跨膜电位以及细胞活性氧（ROS）水平的影响，Western blot检测SM 1044对MAPK（ERK、JNK）信号通路以及PML/RARα融合蛋白的影响和凋亡相关蛋白表达的变化。.. SM 1044能够显著诱导NB4-R1细胞发生细胞凋亡以及线粒体跨膜电位丢失，同时能活化凋亡相关蛋白caspase-3、caspase-8、caspase-9以及抗多腺苷二磷酸核糖聚合酶；SM 1044可诱导NB4-R1细胞产生ROS；Western blot检测结果显示，SM 1044能够激活MAPK（ERK、JNK）信号通路的磷酸化，同时下调PML/RARα融合蛋白的表达。.. SM 1044能够诱导全反式维甲酸耐药急性早幼粒细胞白血病细胞株NB4-R1细胞凋亡，其诱导凋亡可能与ROS/ERK以及ROS/JNK信号通路有关，此外，SM 1044也可通过下调PML/RARα融合蛋白诱导细胞凋亡。.

Topics: Apoptosis; Cell Differentiation; Cell Line; Humans; Leukemia, Promyelocytic, Acute; Oncogene Proteins, Fusion; Reactive Oxygen Species; Tretinoin

Activation of hepatic stellate cells (HSCs) is a pivotal event in liver fibrosis, characterized by enhanced retinoic acid signals. Although up-regulated retinoic acid signal responds further to maintain HSC activation, the underlying molecular mechanisms are largely unknown. In this study, we sought to investigate the role of lncRNA-H19 in regulation of retinoic acid signals, and to further examine the underlying mechanism in this molecular context. We found that lncRNA-H19 upregulation could enhance retinoic acid signals to induce HSC activation, whereas lncRNA-H19 knockdown completely disturbed retinoic acid signals. Moreover, the activation of retinoic acid signals impaired the lncRNA-H19 knockdown mediated HSC inactivation. Interestingly, we also found that enhanced retinoic acid signals by lncRNA-H19 was associated with a coordinate increase in retinol metabolism during HSC activation. Increased retinol metabolism contributed to obvious lipid droplet consumption. Importantly, we identified that alcohol dehydrogenase III (ADH3) was essential for lncRNA-H19 to enhance retinoic acid signals. The inhibition of ADH3 completely abrogated the lncRNA-H19 mediated retinoic acid signals and HSC activation. Of note, we identified dihydroartemisinin (DHA) as a natural inhibitor for lncRNA-H19. Treatment with DHA significantly decreased the expression of lncRNA-H19, reduced the expression of ADH3, blocked retinoic acid signals, and in turn, inhibited HSC activation. Overall, these results provided novel implications to reveal the molecular mechanism of increased retinoic acid signals during HSC activation, and identify lncRNA-H19/ADH3 pathway as a potential target for the treatment of liver fibrosis.

Topics: Aldehyde Oxidoreductases; Animals; Artemisinins; Carbon Tetrachloride; Cell Line; Gene Knockdown Techniques; Hepatic Stellate Cells; Lipid Metabolism; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred ICR; Receptors, Retinoic Acid; RNA, Long Noncoding; Signal Transduction; Tretinoin; Vitamin A