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Recently, we reported that 3-amino-6-(3-aminopropyl)-5,6-dihydro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline (AM6-36), sharing structural similarity with naturally occurring isoquinolines, induced activities mediated by retinoid X receptor (RXR) response element accompanied by antiproliferative effects on breast cancer cells. To further characterize the biologic potential of AM6-36, we currently report studies conducted with HL-60 human leukemia cells. AM6-36 significantly inhibited cellular proliferation in a dose- and time-dependent manner with an IC(50) value of 86 nM. When evaluated at low test concentrations (≤0.25 μM), AM6-36 induced arrest in the G2/M phase of the cell cycle. At higher concentrations (1 and 2 μM), the response shifted to apoptosis, which was consistent with the effect of AM6-36 on other apoptotic signatures including an increase of apoptotic annexin V(+) 7-AAD(-) cells, loss of mitochondrial membrane potential, induction of poly(ADP-ribose) polymerase cleavage, and activation of several caspases. These apoptotic effects are potentially due to up-regulation of p38 MAPK and JNK phosphorylation and down-regulation of c-Myc oncogene expression. Taken together, AM6-36 might serve as an effective anticancer agent by inducing G2/M cell cycle arrest and apoptosis through the activation of MAPKs and inhibition of c-Myc.  相似文献
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From the organic extracts of two Guam sponges, Rhaphoxya sp. and Suberea sp., determined to have cytotoxic and chemopreventive activities, three new compounds, theonellin isocyanate (1) and psammaplysins I and J (5, 6), and six previously reported compounds (2-4, 7-9) were isolated and characterized spectroscopically ((1)H and (13)C NMR, MS, IR, UV, [α](D)). The two new metabolites (5 and 6) isolated from the Suberea sp. sponge are rare examples of compounds containing a bromotyramine moiety rather than the more usual dibromo analogue. For the compounds isolated from the Rhaphoxya sp., this is the first report of the known compounds 2-4 being found in a single sponge. For previously reported compounds 2-4 complete unambiguous (1)H and (13)C NMR data are provided.  相似文献
3.
Traditional medicinal plants are often used for both the prevention and the treatment of local diseases. Taking into consideration the medicinal importance of Hedera nepalensis within local Pakistani traditions, the present study was undertaken to analyze the in vitro cancer chemopreventive and cytotoxic properties of the plant. The in vitro cancer chemopreventive testing was performed using nitrite assay, NFκB assay, aromatase assay, and quinone reductase 1 (QR1) assay. The cytotoxic potential was evaluated on three cancer‐cell lines: MCF‐7, MDA‐MB‐231, and HeLa using sulforhodamine B (SRB) assay. The results of cancer chemopreventive assays show that n‐hexane and ethyl acetate fractions of tested plant have promising cancer chemopreventive potential. Lupeol isolated from n‐hexane as well as ethyl acetate fraction showed lowest IC50 (0.20 ± 1.9 μM) in NFκB assay. Crude extract and its fractions inhibited the growth of three cancer cell lines by more than 60%, IC50 value of lupeol varied from 2.32 to 10.2 μM. HPLC‐DAD‐based quantification of lupeol in different plant tissues demonstrated that leaves of H. nepalensis are a rich source of lupeol (0.196 mg/100 mg dry weight). Our data have shown that H. nepalensis harbors cancer chemopreventive and cytotoxic agents. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献
4.
Kava is a soporific, anxiolytic and relaxant in widespread ritual and recreational use throughout the Pacific. Traditional uses of kava by indigenous Pacific Island peoples reflect a complex pharmacopeia, centered on GABA‐ergic effects of the well‐characterized kavalactones. However, peripheral effects of kava suggest active components other than the CNS‐targeted kavalactones. We have previously shown that immunocytes exhibit calcium mobilization in response to traditionally prepared kava extracts, and that the kavalactones do not induce these calcium responses. Here, we characterize the complex calcium‐mobilizing activity of traditionally prepared and partially HPLC‐purified kava extracts, noting induction of both calcium entry and store release pathways. Kava components activate intracellular store depletion of thapsigargin‐sensitive and ‐insensitive stores that are coupled to the calcium release activated (CRAC) current, and cause calcium entry through non‐store‐operated pathways. Together with the pepper‐like potency reported by kava users, these studies lead us to hypothesize that kava extracts contain one or more ligands for the transient receptor potential (TRP) family of ion channels. Indeed, TRP‐like conductances are observed in kava‐treated cells under patch clamp. Thus TRP‐mediated cellular effects may be responsible for some of the reported pharmacology of kava. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献
5.
Two neolignans, 4′‐methoxymagndialdehyde (1) and magnaldehyde B (2), were isolated from the stem bark of Magnolia officinalis (Magnoliaceae), evaluated for apoptosis‐inducing effects in human cervical epitheloid carcinoma HeLa cells. The apoptosis‐inducing activity of compounds 1 and 2 were assessed by DNA content using flow cytometric analysis. In the immunoblotting analysis, the treatment with 1 and 2 resulted in the cleavage of procaspase‐8 and ‐3 and poly(ADP‐ribose)polymerase into active forms. In addition, in vivo, the administration of 2 to Lewis lung carcinoma‐inoculated mice evidenced a significant inhibition of tumor growth (volume) with reduction of 28.7% at concentration of 20 mg/kg, as compared with the control mice. These findings suggest that 2 can inhibit the proliferation of tumor cells, and might be an anti‐tumoric agent. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献
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