BackgroundMultiple myeloma (MM) is a disease of cell cycle dysregulation while cell cycle modulation can be a target for MM therapy. In this study we investigated the effects and mechanisms of action of a sesquiterpene lactone 6-O-angeloylplenolin (6-OAP) on MM cells.Methodology/Principal FindingsMM cells were exposed to 6-OAP and cell cycle distribution were analyzed. The role for cyclin B1 to play in 6-OAP-caused mitotic arrest was tested by specific siRNA analyses in U266 cells. MM.1S cells co-incubated with interleukin-6 (IL-6), insulin-like growth factor-I (IGF-I), or bone marrow stromal cells (BMSCs) were treated with 6-OAP. The effects of 6-OAP plus other drugs on MM.1S cells were evaluated. The in vivo therapeutic efficacy and pharmacokinetic features of 6-OAP were tested in nude mice bearing U266 cells and Sprague-Dawley rats, respectively. We found that 6-OAP suppressed the proliferation of dexamethasone-sensitive and dexamethasone-resistant cell lines and primary CD138+ MM cells. 6-OAP caused mitotic arrest, accompanied by activation of spindle assembly checkpoint and blockage of ubiquitiniation and subsequent proteasomal degradation of cyclin B1. Combined use of 6-OAP and bortezomib induced potentiated cytotoxicity with inactivation of ERK1/2 and activation of JNK1/2 and Casp-8/-3. 6-OAP overcame the protective effects of IL-6 and IGF-I on MM cells through inhibition of Jak2/Stat3 and Akt, respectively. 6-OAP inhibited BMSCs-facilitated MM cell expansion and TNF-α-induced NF-κB signal. Moreover, 6-OAP exhibited potent anti-MM activity in nude mice and favorable pharmacokinetics in rats.Conclusions/SignificanceThese results indicate that 6-OAP is a new cell cycle inhibitor which shows therapeutic potentials for MM.
Of the 3 common wild grapes-Vitis thunbergii, V. flexuosa, and V. kelungeusis, the extracts or phytochemicals, derived from the V. thunbergii stems have excellent antioxidant properties, so they have great potential as a basis for natural health products that seek to prevent diseases caused by the overproduction of radicals.
The objective of this study is to assess antioxidant activities of methanolic extracts from the leaves of 18 indigenous tree species in Taiwan. Results revealed that, among 18 species, Acer oliverianum exhibited the best free radical scavenging activities. The IC50 values were 5.8 and 11.8 μg/mL on DPPH radical and superoxide radical scavenging activities, respectively. In addition, A. oliverianum also exhibited the strongest ferrous ion chelating activity. Based on a bioactivity-guided isolation principle, the resulting methanolic crude extracts of A. oliverianum leaves were fractionated to yield soluble fractions of hexane, EtOAc, BuOH, and water. Of these, the EtOAc fraction had the best antioxidant activity. Furthermore, 8 specific phytochemicals were isolated and identified from the EtOAc fraction. Among them, 1,2,3,4,6-O-penta-galloyl-β-D-glucopyranose had the best free radical scavenging activity. These results demonstrate that methanolic extracts and their derived phytochemicals of A. oliverianum leaves have excellent antioxidant activities and thus they have great potential as sources for natural health products.
The fabrication and placement of high purity nanometals, such as one-dimensional copper (Cu) nanowires, for interconnection in integrated devices have been among the most important technological developments in recent years. Structural stability and oxidation prevention have been the key issues, and the defect control in Cu nanowire growth has been found to be important. Here, we report the synthesis of defect-free single-crystalline Cu nanowires by controlling the surface-assisted heterogeneous nucleation of Cu atomic layering on the graphite-like loop of an amorphous carbon (a-C) lacey film surface. Without a metal-catalyst or induced defects, the high quality Cu nanowires formed with high aspect ratio and high growth rate of 578 nm/s. The dynamic study of the growth of heterogeneous nanowires was conducted in situ with a high-resolution transmission electron microscope. The study illuminates the new mechanism by heterogeneous nucleation control and laying the groundwork for better understanding of heterosurface-assisted nucleation of defect-free Cu nanowire on a-C lacey film.
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