Increased expression of amyloid precursor protein promotes proliferation and migration of AML1/ETO-positive leukemia cells and be inhibited by panobinostat.

Amyloid precursor protein (APP) is a highly conserved integral membrane protein extensively expressed in various types of cells. Previously we found that overexpression of APP in patients with AML1/ETO-positive acute myeloid leukemia (AML) associated with a higher incidence of extramedullary infiltrationin and indicate a poor prognosis. In this study, we attempted to define the roles of APP in AML1/ETO-positive leukemia cells. Western blotting and qRT-PCR analysis showed that protein levels of APP are significantly higher in Kasumi-1, a t(8;21)/ AML1/ETO-positive M2-type AML cell line. Stable knockdown of APP by lentivirus-based RNA interference (RNAi) dramatically impaired colony-formation and migration ability of Kasumi-1 cells, whereas APP knockdown had very little effect on cell viability, apoptosis, cell cycle and differentiation. We further explored whether the pan-histone deacetylase inhibitor panobinostat could deplete the protein levels of APP in Kasumi-1 cells. Treatment with panobinostat caused depletion of APP in Kasumi-1 cells. These findings indicate that overexpression of APP is involved in promoting proliferation and migration of AML1/ETO-positive leukemia cells and can be inhibited by panobinostat, which provide an attractive prospect for treatment of AML1/ETO-positive AML.

Four new naphthylisoquinoline alkaloids from Ancistrocladus tectorius.

Four new naphthylisoquinoline alkaloids, ancistrotectoriline A (1), ancistrotectoriline B (2), 6-O-methyl-4'-O-demethylancistrocladine (3), and 6-O-methyl-4'-O-demethylhamatine (4), were isolated from the stems and leaves of Ancistrocladus tectorius, collected from Hainan Province, Southern China. Their structures were elucidated using MS and NMR methods.

Studies on bioactive components from Chinese medicinal plants.

Several novel bioactive components isolated from Chinese medicinal plants will be presented. These include novel maytansinoid tumor inhibitors, some new ent-kaurane and rosane diterpenoids from Mallotus anomalus Meer et Chun (Euphorbiaceae), as well as novel insecticide, stemona alkaloids from Stemona parviflora C. H. Wright (Stemonaceae). Both are native plants of Hainan island, China. 2D NMR techniques such as mono and hetero-COSY, NOESY, COLOC as well as 1H-NMR line broadening effect were utilized for structure elucidation. The separation techniques, structure elucidations and bioassay results will be reported.