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排序方式: 共有3707条查询结果,搜索用时 15 毫秒
1.
David Kessel 《Autophagy》2015,11(10):1941-1943
The high degree of selectivity for photodamage to subcellular organelles can provide a means for evaluation of autophagic death pathways. While many current reports rely on ambiguous criteria, there are glimmers of unequivocal evidence. 相似文献
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A novel microtubule depolymerizing colchicine analogue triggers apoptosis and autophagy in HCT‐116 colon cancer cells 下载免费PDF全文
Ashok Kumar Baljinder Singh Parduman R. Sharma Sandip B. Bharate Ajit K. Saxena D. M. Mondhe 《Cell biochemistry and function》2016,34(2):69-81
Colchicine is a tubulin‐binding natural product isolated from Colchicum autumnale. Here we report the in vitro anticancer activity of C‐ring modified semi‐synthetic derivative of colchicine; N‐[(7S)‐1,2,3‐trimethoxy‐9‐oxo‐10‐(4‐phenyl‐piperidin‐1‐yl)‐5,6,7,9 tetrahydrobenzo[a]heptalen‐7‐yl]acetamide ( 4h ) on colon cancer HCT‐116 cell line. The compound 4h was screened for anti‐proliferative activity against different human cancer cell lines and was found to exhibit higher cytotoxicity against colon cancer cell lines HCT‐116 and Colo‐205 with IC50 of 1 and 0.8 μM respectively. Cytotoxicity of the compound to the normal fR2 breast epithelial cells and normal HEK293 human embryonic kidney cells was evaluated in concentration and time‐dependent manner to estimate its selectivity for cancer cells which showed much better selectivity than that of colchicine. Compound 4h induced cell death in HCT‐116 cells by activating apoptosis and autophagy pathways. Autophagy inhibitor 3‐MA blocked the production of LC3‐II and reduced the cytotoxicity in response to 4h , but did not affect apoptosis, suggesting thereby that these two were independent events. Reactive oxygen species scavenger ascorbic acid pretreatment not only decreased the reactive oxygen species level but also reversed 4h induced cytotoxicity. Treatment with compound 4h depolymerized microtubules and the majority of cells arrested at the G2/M transition. Together, these data suggest that 4h has better selectivity and is a microtubule depolymerizer, which activates dual cell‐death machineries, and thus, it could be a potential novel therapeutic agent in cancer therapy. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
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The conditioned medium from osteo‐differentiating human mesenchymal stem cells affects the viability of triple negative MDA‐MB231 breast cancer cells 下载免费PDF全文
This study aimed to investigate the effect of conditioned media (CM) from osteo‐differentiating and adipo‐differentiating human mesenchymal stem cells (MSCs) isolated from lipoaspirates of healthy female donors on the viability of triple‐negative breast cancer cells MDA‐MB231. The CM of undifferentiated and differentiating MSCs were collected after 7, 14, 21 and 28 days of culture. The effects of MSC CM on cell proliferation were assessed using an 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay after 24 h. The effects of osteo‐differentiating cell CM on apoptotic promotion, cell cycle impairment, mitochondrial transmembrane potential dissipation, production of reactive oxygen species and autophagosome accumulation were analysed by flow cytometry and Western blot. MTT assay showed that only CM collected from osteo‐induced cells at day 28 (d28O‐CM) reduced tumour cell viability. Treatment with d28O‐CM restrained cell cycle progression through G2 phase, elicited a caspase‐8‐driven apoptotic effect already after 5 h of culture, and down‐regulated autophagosome accumulation and beclin‐1 expression. The finding that factor(s) secreted by osteo‐differentiating MSCs shows properties of an apoptotic inducer and autophagy inhibitor on triple‐negative breast cancer cells may have an important applicative potential that deserves further investigation. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
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《Molecular cell》2020,77(2):228-240.e7
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Ana?s Pujals Lo?titia Favre Catherine Pioche-Durieu Aude Robert Guillaume Meurice Marion Le Gentil Sonia Chelouah Nadine Martin-Garcia Eric Le Cam Catherine Guettier Martine Rapha?l Lyubomir T Vassilev Philippe Gaulard Patrice Codogno Marc Lipinski Jo?lle Wiels 《Autophagy》2015,11(12):2275-2287
The Epstein-Barr virus (EBV) is associated with various lymphoproliferative disorders and lymphomas. We have previously demonstrated that treating wild-type TP53-expressing B cell lines with the TP53 pathway activator nutlin-3 induced apoptosis in EBV-negative and EBV-positive latency I cells whereas EBV-positive latency III cells remained much more apoptosis-resistant. Here, we report a constitutively high level of autophagy in these resistant cells which express high levels of the proautophagic protein BECN1/Beclin 1 based, at least in part, on the activation of the NFKB signaling pathway by the viral protein LMP1. Following treatment with nutlin-3, several autophagy-stimulating genes were upregulated both in EBV-negative and EBV-positive latency III cells. However the process of autophagy was only triggered in the latter and was associated with an upregulation of SESN1/sestrin 1 and inhibition of MTOR more rapid than in EBV-negative cells. A treatment with chloroquine, an inhibitor of autophagy, potentiated the apoptotic effect of nutlin-3, particularly in those EBV-positive cells which were resistant to apoptosis induced by nutlin-3 alone, thereby showing that autophagy participates in this resistant phenotype. Finally, using immunohistochemical staining, clinical samples from various B cell lymphoproliferations with the EBV-positive latency II or III phenotype were found to harbor a constitutively active autophagy. 相似文献
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Kelly D Sullivan Vignesh V Palaniappan Joaquín M Espinosa 《Cell cycle (Georgetown, Tex.)》2015,14(1):56-63
Despite extensive study, the mechanisms of cell fate choice upon p53 activation remain poorly understood. Using genome-wide shRNA screening, we recently identified the ATM kinase as synthetic lethal with Nutlin-3, an MDM2 inhibitor that leads to non-genotoxic p53 activation. Here, we demonstrate that while this synthetic lethal interaction relies upon components of both the intrinsic and extrinsic apoptotic pathways (e.g., BAX and BID), it is not due to significant ATM effects on the expression of p53 target genes. Instead, loss of ATM activity results in increased mitochondria and reactive oxygen species that drive apoptosis. Finally, we provide evidence that pharmacologic inhibition of ATM blocks autophagy in direct opposition to p53, which activates this process, and that inhibition of autophagy is sufficient to elicit an apoptotic response when combined with Nutlin-3. 相似文献