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1.
Inhibition of haringtonine-induced apoptosis by tetradecanoylphorbol acetate in human leukemia HL-60
目的:研究十四酰佛波乙酸酯(TA)预处理后,三尖杉酯碱(Har)和喜树碱(Cam)诱导人白血病HL60细胞凋亡的变化.方法:染色质凝集观察,流式细胞术,DNA琼脂糖凝胶电泳和点杂交.结果:TA200nmol·L-1预处理HL60细胞6h,明显抑制Har01mg·L-1作用3h诱导的细胞凋亡,但只部分抑制Cam02mg·L-1作用3h诱导的细胞凋亡.TA预处理HL60细胞明显降低cmyc基因的表达.结论:TA明显抑制由Har和部分抑制由Cam诱导的HL60细胞凋亡,而且TA预处理的细胞中cmyc基因表达明显下降,这可能导致了对诱导细胞凋亡的抑制. 相似文献
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Induction of apoptosis in human promyelocytic leukemia HL-60 cells by α-anordrin was estimated with the use of morphological and biochemical methods. α-Anordrin 2.5-50.0 μmol·L-1 inhibited the growth of HL-60 cells in a dose-dependent manner and arrested them at G1 phase of cell cycle. The cells exhibited marked morphological changes such as cell shrinkage, nuclear fragmentation, chromatin condensation. Agarose gel electrophoresis of DNA extracted from α-anordrin-treated cells revealed a “ladder” pattern. Nearly 63% of cells underwent apoptosis at α-anordrin concentration of 50 μmol·L-1 as determined by flow cytometry. The data demonstrate that α-anordrin induces HL-60 cell apoptosis, which might be related to its antitumor action. 相似文献
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目的:研究槲皮素对人白血病HL60细胞bcl2基因表达的影响.方法:采用免疫组织化学技术和RNA点杂交观察基因表达.结果:Que15-60μmol·L-1处理HL60细胞48h使bcl2蛋白由对照组的94%表达下调到45%-84%,并能明显下调HL60细胞bcl2mRNA表达.结论:Que诱导HL60细胞凋亡,其诱导凋亡的分子机制与下调bcl2基因表达有关. 相似文献
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José Roberto Oliveira Ferreira Bruno Coêlho Cavalcanti Patricia Marçal da Costa Francisco Frederico Perlinson de Arantes Elson Santiago de Alvarenga Célia Regina Alvares Maltha Luiz Cláudio de Almeida Barbosa Gardenia Carmen Gadelha Militão Claúdia Pessoa Paulo Michel Pinheiro Ferreira 《Toxicology in vitro》2013,27(5):1458-1466
Sesquiterpene lactones (SLs) are natural products with a variety of biological activities. Previously, we demonstrated the cytotoxic effects of three new α-santonin derivatives on different tumor cell lines with low toxic effects upon peripheral human leukocytes. Here, we evaluated the mechanism of action triggered by these derivatives. HL-60 cell cycle determined after 24 h treatment revealed a significant inhibition on cell-cycle progression and leading to an increasing of cells in G2/M [7.6% and 9.0% for compound 3% and 9.0% and 8.6% for compound 4 (1 and 2 μM, respectively)]. However, after 48 h exposure, all compounds caused G2/M reduction and a significant DNA fragmentation. Compounds 2, 3 and 4 were able to induce apoptosis on leukemia cells, which was corroborated by phosphatidyserine externalization and activation of caspases-3 and -7 after 24 h exposure. None of the derivatives analyzed caused depolarization of mitochondrial membrane within 24 h of incubation, suggesting the involvement of the extrinsic apoptotic pathway in the death process. The antiproliferative action of these compounds is related to the DNA synthesis inhibition and cell cycle arrest, which probably lead to apoptosis activation. Therefore, these santonin derivatives are promising lead candidates for development of new cytotoxic agents. 相似文献
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RM, a novel aminosteroid synthesized by our research group, shows a broad spectrum of antitumor activity against nine cancer
cell lines and limited toxicity against two normal cell lines. However, its related mechanism of action has not yet been elucidated.
In this study, we investigated the cellular and molecular events underlying the cytotoxicity of RM in human acute promyelocytic
leukemia HL-60 cells. RM was found to induce a G0/G1 cell cycle block of HL-60 cells but not terminal myeloid differentiation.
Interestingly, typical apoptotic morphological changes were exhibited by HL-60 cells treated with RM stained with Hoechst
33342 and examined by fluorescence microscopy. Apoptotic death assay using annexin-V/propidium iodide dual staining flow cytometry
demonstrated a dose-dependent apoptotic effect of RM on HL-60 cells. In addition, RM induced the cleavage of caspase-3, caspase-8
and PARP, but not the cleavage of caspase-9. Our findings suggest that RM reduces HL-60 cells survival through a caspase-dependent
death receptor pathway. 相似文献
7.
Masayuki Ninomiya Kyohei Nishida Kaori Tanaka Kunitomo Watanabe Mamoru Koketsu 《Journal of natural medicines》2013,67(3):460-467
Flavonoids are widely occurring polyphenols that are found in plants. The aim of this study was to investigate the structure–activity relationships of 5,7-dihydroxyflavones, with a focus on the effect of B ring structure substitution on the antiproliferative effects of the compounds in human leukemia HL-60 cells. We prepared a series of 5,7-dihydroxyflavones and evaluated their ability to inhibit the proliferation of HL-60 cells by using the MTT assay. The apoptosis- and cell differentiation-inducing ability of the most potent flavones were investigated using staining and morphological analyses. This study explored the antileukemic and chemopreventive potency of 5,7-dihydroxyflavones, particularly diosmetin and chrysoeriol, which have both hydroxy and methoxy groups on the B ring. 相似文献
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Shoji K Tsubaki M Yamazoe Y Satou T Itoh T Kidera Y Tanimori Y Yanae M Matsuda H Taga A Nakamura H Nishida S 《Archives of pharmacal research》2011,34(3):469-475
Mangiferin, 1,3,6,7-tetrahydroxyxanthone-C2-β-D: -glucoside (C-glucosylxanthone), is a xanthone derivative that is widely distributed in higher plants. Recently, mangiferin was found to exhibit potential antitumor effects. However, the molecular mechanisms of this effect have not been elucidated. In the present study, we attempt to clarify the mechanism of mangiferin-induced apoptosis in the human acute myeloid leukemia cell line HL-60; mangiferin was found to induce apoptosis. We also observed a concurrent increase in caspase-3 activity and DNA fragmentation. Furthermore, on examining the survival signals expressed during apoptotic induction, we observed that mangiferin caused a remarkable decrease in the nuclear entry of NF-κB p65. However, there were no changes in the expression of other survival signals, such as extracellular signal-regulated kinase 1/2, protein kinase B, and p38 mitogenactivated protein kinase. In addition, mangiferin suppressed the expressions of Bcl-xL and XIAP; however, we did not note any changes in the levels of Bcl-2, Bax, and Bim. These results indicate that mangiferin induces apoptosis by suppressing NF-κB activation and expressions of Bcl-xL and XAIP. These findings suggest that mangiferin may be useful as an anticancer agent and can be used in combination therapy with other anticancer drugs for the treatment of acute myeloid leukemia. 相似文献
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OBJECTIVE: To elucidate the toxicological properties of silica nanoparticles (nano-SiO2) by investigating their effect on human peripheral blood mononuclear cells (PBMCs). METHODS: The particle size, morphology and dispersion of nano-SiO2 were characterized by the transmission electron microscope. Human blood samples were provided by 6 healthy volunteers, while PBMCs were isolated from the peripheral blood cells and cultured in vitro. The cells were treated with 10 nm nano-SiO2 in RPMI 1640 media at the concentration of 0 (normal control), 12.5, 25, 50, 100 and 200 mg·L-1 for 24 h. Blood routine examination was performed. The human PBMC morphology was observed under an inverted microscope, followed by detection and analysis of the microfilament using TRITC-phallodin and fluorescence microscopy, respectively. After staining with Annexin V-FITC and propidumiodide, the cell early apoptosis rate was measured by flow cytometry. Reactive oxygen species (ROS) production in the supernatant medium liquid was measured with ELISA. RESULTS: Compared with normal control group, the proportion of lymphocytes and macrophages significantly decreased when the cells were treated with nano-SiO2 100 and 200 mg · L-1. The cell morphology changed and the microfilament was disrupted. The early apoptosis rate and intracellular ROS level both significantly increased along with the nano-SiO2 exposure concentration (P<0.01). In addition, there was a significant positive correlation between ROS and apoptosis rate (R2=0.847, P<0.01). CONCLUSION: Nano-SiO2 demonstrates cytotoxicity when exposed to PBMCs. The elevated level of oxidative stress is probably a major reason for early apoptosis. 相似文献
10.
研究蛋白质合成抑制剂环己米特(cicloheximide,Cic)对α双炔失碳酯(αanordrin,Ano)诱导的白血病K562细胞凋亡的影响.方法:荧光显微镜观察形态学变化;流式细胞仪检测DNA含量;琼脂糖凝胶电泳分析DNA断裂.结果:Ano50μmol·L-1处理K562细胞24小时诱导细胞凋亡.Cic1μmol·L-1共同处理不能减弱或延缓Ano的这一作用.相反,Cic明显增强Ano诱导的细胞凋亡.Cic100μmol·L-1本身诱导25%K562细胞凋亡.结论:Ano诱导的K562细胞凋亡不依赖于新的蛋白质合成. 相似文献
11.
M.A Moosavi S. Moasses Ghafary I. Asvadi-Kermani H. Hamzeiy M. Rahmati A.H. Ahmadi A. Nikanfar Z. Sanaat M. Asadi-Khiavi 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2011,19(6):455-461
Background and the purpose of the study
Leukemia is a malignant disorder of the blood progenitor/stem cells which is characterized by abnormal proliferation of white blood cells. Although anti-cancer drugs induce apoptosis in cancerous cells, drug resistance is the significant problem mainly due to over-expression of inhibitors of apoptosis proteins (IAPs) such as survivin. In this content, it has been reported that an anti-inflammatory drug, Carbenoxolone (CBX), could induce apoptosis and growth inhibition in several types of cancerous cells. In the present study, effects of CBX on apoptosis and level of the expression of survivin gene and its ΔEx3 splicing variant have were evaluated in K562 cells.Methods
K562 cells were cultured and treated with different concentrations of CBX (50-300 µM) at different time intervals (12-48 hrs). Trypan blue exclusion test was used to evaluate cell viability. Fluorescent microscopy (Acridine Orange/Ethidium Bromide double staining) and DNA fragmentation assay were used to study apoptosis. The expression level of survivin and its ΔEx3 splice variant were studied by RT-PCR.Results and Major Conclusion
It was found that both growth inhibition and apoptosis occurred in K562 cells. In addition, down-regulation of survivin and survin-ΔEx3 were observed, after 2-4 hrs treatment with 150 µM of CBX. However, the expression level of survivin and its ΔEx3 splice variant increased in subsequent time (6-12 hrs) nearly to the level of control cells. From the results of this study, it may be concluded that CBX can be considered as a candidate for further studies in CML treatment, especially in the case of drug-resistant leukemia cells. 相似文献12.
AIM: The differentiation capability of guanosine 5'-triphosphate (GTP) was studied using U937 and KG1 cells. METHODS: Cell cycle was analyzed by PI staining using flow cytometry. Apoptosis was measured by Annexin-V-FITC/PI double staining using flow cytometry. Differentiation was observed by morphological criteria, Wright-Giemsa staining and expression of cell surface markers CD11b and CD14. RESULTS: Variable GTP concentrations (25-200 micromol/L) at short treatment times (up to 24 h) showed significant anti-proliferative activities among both cell types. However, longer treatment times (up to 72 h) were required to trigger apoptosis. Cell-cycle analyses of the GTP-treated cells indicated an increase in S-phase population by 48 h followed by the appearance of a sub-G(1) peak after 72 h of treatment. The effects of GTP on U937 and KG1 cells were accompanied with differentiation toward monocyte/macrophage lineage. This was evidenced by a sharp increase in the extent of CD11b and CD14 expression after 24 h of exposure to GTP. The viability of both cell types did not significantly change during the first 24 h. However, at longer treatment times (72-96 h), dramatic decreases in both the extent of CD14 expression and the cell viabilities were observed. Simultaneous measurement of apoptosis and CD14 expression in GTP-treated U937 cells indicated that cells with lower CD14 content underwent more apoptosis. CONCLUSION: These finding may pave the way for further pharmaceutical evaluation of GTP as a suitable differentiating agent for acute myeloblastic leukemia (AML) therapy. 相似文献
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Aim:
To investigate the effect of genipin on apoptosis in human leukemia K562 cells in vitro and elucidate the underlying mechanisms.Methods:
The effect of genipin on K562 cell viability was measured using trypan blue dye exclusion and cell counting. Morphological changes were detected using phase-contrast microscopy. Apoptosis was analyzed using DNA ladder, propidium iodide (PI)-labeled flow cytometry (FCM) and Hoechst 33258 staining. The influence of genipin on cell cycle distribution was determined using PI staining. Caspase 3 activity was analyzed to detect apoptosis at different time points. Protein levels of phospho-c-Jun, phosphor-c-Jun N-terminal kinase (p-JNK), phosphor-p38, Fas-L, p63, and Bax and the release of cytochrome c were detected using Western blot analysis.Results:
Genipin reduced the viability of K562 cells with an IC50 value of approximately 250 μmol/L. Genipin 200–400 μmol/L induced formation of typical apoptotic bodies and DNA fragmentation. Additionally, genipin 400 μmol/L significantly increased the caspase 3 activity from 8–24 h and arrested the cells in the G2/M phase. After stimulation with genipin 500 μmol/L, the levels of p-JNK, p-c-Jun, Fas-L, Bax, and cytochrome c were remarkably upregulated, but there were no obvious changes of p-p38. Genipin 200–500 μmol/L significantly upregulated the Fas-L expression and downregulated p63 expression. Dicoumarol 100 μmol/L, a JNK1/2 inhibitor, markedly suppressed the formation of apoptotic bodies and JNK activation induced by genipin 400 μmol/L.Conclusion:
These results suggest that genipin inhibits the proliferation of K562 cells and induces apoptosis through the activation of JNK and induction of the Fas ligand. 相似文献17.
Effect of quercetin on cell cycle of HL-60 cells 总被引:2,自引:0,他引:2
本文报道了槲皮素对人早幼粒白血病细胞株HL-60细胞的增殖和细胞周期的影响.结果表明槲皮素能抑制HL-60细胞的增殖,呈剂量依赖关系,当槲皮素作用24,48,72h后,其IC50分别为46.6,28.7,14.9μmol·L-1.流式细胞仪分析表明,槲皮素能明显增加HL-60的G2-M期细胞,而相对减少G0/G1细胞之百分比,且呈剂量依赖关系,当去除槲皮素时,该作用是可逆的.结果表明槲皮素对肿瘤细胞的生长抑制作用可能与其对细胞周期的影响有关. 相似文献
18.
《Toxicology in vitro》2010,24(6):1504-1511
Solamargine (SM), a steroidal alkaloid glycoside from Solanum nigrum L., displayed a superior cytotoxicity to many human tumor cells. Further investigation with human K562 leukemia cells found that SM could induce an early lysosomal rupture within 2 h as assessed by acridine-orange relocation and alkalinization of lysosomes. Intracellular lysosomal rupture is also confirmed with the release of cathepsin B to cytosol detected by western blot. Subsequent mitochondrial damage including mitochondrial membrane permeabilization detected by decrease membrane potential as well as the release of cytochrome c from mitochondria was also observed. The cellular Ca2+ overload is more pronounced in SM-treated cells. Cells exposed to 10 μM SM for 30 min showed a maximum 7-fold increase in intracellular calcium concentration compared with vehicle-treated controls. The down-expression of Bcl-2, up-regulation of Bax, caspase-3 and caspase-9 activities followed by above changes revealed that the cytotoxicity of SM was involved in a lysosomal–mitochondrial death pathway induced by SM. 相似文献
19.
Cheng Bin Liu Li-Hua Chen An-Chin ChengWei-Jen Chen Mei-Ling TsaiYumei Liu Chi-Tang HoMin-Hsiung Pan 《Food and chemical toxicology》2011,49(4):1033-1042
Hexahydro-β-acids (HBA) and β-acids (BA) displayed strong growth inhibitory effects against human leukemia HL-60 cells and were able to induce apoptosis in a concentration- and time-dependent manner and the morphological changes associated with apoptotic cell death; however, BA was less effective. Treatment with HBA caused a rapid loss of mitochondrial trans-membrane potential, release of mitochondrial cytochrome c into cytosol. The levels of Bad and Bax were dramatically increased in cells treated with HBA. In addition, the results showed that HBA promoted the up-regulation of Fas prior to the processing and activation of pro-caspase-8 and cleavage of Bid, suggesting the involvement of a Fas-mediated pathway in HBA-induced cells. Moreover, the changes occurred after single breaks in DNA were detected, suggesting that HBA induced irreparable DNA damage, which in turn triggered the process of apoptosis. HBA markedly enhanced the growth arrest DNA damage-inducible gene 153 (GADD153) protein in a concentration- and time-dependent manner. These findings suggest that HBA creates an oxidative cellular environment that induces DNA damage and GADD153 gene activation, which in turn triggers apoptosis in HL-60 cells. Our study identified the novel mechanisms of HBA-induced apoptosis and indicated that HBA may be used as a potential chemopreventive and chemotherapeutic agent. 相似文献
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Zhiying Yu Fangling Wu Liang Chen Qian Li Chaojie Wang Jinhua Dong Song-qiang Xie 《药学学报(英文版)》2014,4(6):424-429
Arsenic trioxide (ATO) has been identified as an effective treatment for acute promyelocytic leukemia (APL) but is much less effective against solid tumors such as hepatocellular carcinoma (HCC). In the search for ways to enhance its therapeutic efficacy against solid tumors, we have examined its use in combination with a novel derivative of β-elemene, N-(β-elemene-13-yl)tryptophan methyl ester (ETME). Here we report the effects of the combination on cell viability, apoptosis, the cell cycle and mitochondria membrane potential (MMP) in HCC SMMC-7721 cells. We found that the two compounds acted synergistically to enhance antiproliferative activity and apoptosis. The combination also decreased the MMP, down-regulated Bcl-2 and pro-proteins of the caspase family, and up-regulated Bax and BID, all of which were reversed by the p53 inhibitor, pifithrin-α. In addition, the combination induced cell cycle arrest at the G2/M phase and reduced tumor volume and weight in an xenograft model of nude mice. Overall, the results suggest that ETME in combination with ATO may be useful in the treatment of HCC patients particularly those unresponsive to ATO alone.Key words: Hepatocarcinoma, β-Elemene derivative, As2O3, Apoptosis, p53 相似文献