Diterpenoids isolated from Labiatae family herbs have strong antitumor activities with low toxicity. In this study, Eriocalyxin B (EriB), a diterpenoid extracted from Isodon eriocalyx, was tested on human leukemia/lymphoma cells and murine leukemia models. Acute myeloid leukemia cell line Kasumi-1 was most sensitive to EriB. Significant apoptosis was observed, concomitant with Bcl-2/Bcl-X L downregulation, mitochondrial instability and caspase-3 activation. AML1-ETO oncoprotein was degraded in parallel to caspase-3 activation. EriB-mediated apoptosis was associated with NF-jB inactivation by preventing NF-jB nuclear translocation and inducing IjBa cleavage, and disturbance of MAPK pathway by downregulating ERK1/2 phosphorylation and activating AP-1. Without affecting normal hematopoietic progenitor cells proliferation, EriB was effective on primary t(8;21) leukemia blasts and caused AML1-ETO degradation. In murine t(8;21) leukemia models, EriB remarkably prolonged the survival time or decreased the xenograft tumor size. Together, EriB might be a potential treatment for t(8;21) leukemia by targeting AML1-ETO oncoprotein and activating apoptosis pathways.

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BackgroundSmoking is the leading cause of COPD. Exploring molecular markers and understanding the pathogenic mechanisms of smoking-related COPD are helpful for early clinical diagnosis and treatment of the disease. This study aims to identify specific circulating microRNAs (miRNAs) from the blood of COPD patients with a long history of smoking.MethodsBlood samples from four different groups were collected, and miRNA microarray was performed. Differential expression of miRNAs was verified by quantitative polymerase chain reaction. In vitro, THP-1 cells were cultured and stimulated with cigarette smoke extract (CSE) or transfected with miR-149-3p inhibitor/mimics. Protein levels of Toll-like receptor 4 (TLR-4) and nuclear factor κB (NF-κB) were detected using Western blot and immunofluorescence. Interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels were determined by an enzyme-linked immunosorbent assay.ResultsmiRNA profiling revealed that the expression of 56 miRNAs was changed between the four groups. Expression of miR-149-3p in group C (non-smoker non-COPD) was higher than in group S (smoker non-COPD), S-COPD (smoker with stable COPD) and AE-COPD (smoker with acute exacerbation COPD). CSE stimulation down-regulated the expression of miR-149-3p and up-regulated the TLR-4 and NF-κB levels in THP-1 cells. Transfecting miR-149-3p inhibitors in THP-1 cells also increased the expression of its target genes. Furthermore, overexpression of miR-149-3p inhibited the TLR-4/NF-κB signaling pathways and reduced the secretion of IL-1β and TNF-α.ConclusionThis study found that smoking can induce differential expression of circulating miR-NAs, such as down-regulation of miR-149-3p. Reducing miR-149-3p may increase the inflammatory response in COPD patients through the regulation of the TLR-4/NF-κB signaling pathway.

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