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Autophagy leukemia

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https://www.readbyqxmd.com/read/29456707/resveratrol-induces-autophagic-apoptosis-via-the-lysosomal-cathepsin-d-pathway-in-human-drug-resistant-k562-adm-leukemia-cells
#1
Zhewen Zhang, Zhuan Liu, Jing Chen, Juan Yi, Juan Cheng, Wangqing Dun, Hulai Wei
The aim of the present study was to investigate the crosstalk between resveratrol (Res)-induced autophagy and apoptosis, and the molecular pathway by which autophagy leads to apoptotic death in drug-resistant K562/ADM leukemia cells. The viability of K562/ADM cells was determined using the MTT assay. The formation of autophagic vacuoles was detected using transmission electron microscopy and monodansylcadaverine (MDC) staining. Cell apoptosis was evaluated using flow cytometry. The expression of apoptosis- or autophagy-associated proteins was measured using western blotting...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29449563/cinacalcet-mediated-activation-of-the-camkk%C3%AE-lkb1-ampk-pathway-attenuates-diabetic-nephropathy-in-db-db-mice-by-modulation-of-apoptosis-and-autophagy
#2
Ji Hee Lim, Hyung Wook Kim, Min Young Kim, Tae Woo Kim, Eun Nim Kim, Yaeni Kim, Sungjin Chung, Young Soo Kim, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Hye Won Kim, Cheol Whee Park
Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca2+ concentration and the phosphorylation of Ca2+ /calmodulin-dependent protein kinase kinaseβ (CaMKKβ)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29446053/systems-pharmacological-analysis-of-mitochondrial-cardiotoxicity-induced-by-selected-tyrosine-kinase-inhibitors
#3
Tanaya Vaidya, Jeff Kamta, Maher Chaar, Anusha Ande, Sihem Ait-Oudhia
Tyrosine kinase inhibitors (TKIs) are targeted therapies rapidly becoming favored over conventional cytotoxic chemotherapeutics. Our study investigates two FDA approved TKIs, DASATINIB; indicated for IMATINIB-refractory chronic myeloid leukemia, and SORAFENIB; indicated for hepatocellular carcinoma and advanced renal cell carcinoma. Limited but crucial evidence suggests that these agents can have cardiotoxic side effects ranging from hypertension to heart failure. A greater understanding of the underlying mechanisms of this cardiotoxicity are needed as concerns grow and the capacity to anticipate them is lacking...
February 14, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29434902/chloroquine-exerts-antitumor-effects-on-nb4-acute-promyelocytic-leukemia-cells-and-functions-synergistically-with-arsenic-trioxide
#4
Shousheng Liu, Xiuyu Cai, Liangping Xia, Chang Jiang, Ping Chen, Xiaopai Wang, Bei Zhang, Hong Yun Zhao
Chloroquine (CQ) has been confirmed to exhibit antitumor effects on different types of cancer cell, but whether it exerts the same effect on acute promyelocytic leukemia (APL) cells remains to be confirmed. In the present study, the effects of various concentrations of CQ on the growth, apoptosis and cell cycle distribution of NB4 cells, as well as the potential mechanisms underlying these effects, were examined. The combined effect of CQ and arsenic trioxide (ATO) on the growth of NB4 cells was also determined...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434216/a-large-scale-rna-interference-screen-identifies-genes-that-regulate-autophagy-at-different-stages
#5
Sujuan Guo, Kevin J Pridham, Ching-Man Virbasius, Bin He, Liqing Zhang, Hanne Varmark, Michael R Green, Zhi Sheng
Dysregulated autophagy is central to the pathogenesis and therapeutic development of cancer. However, how autophagy is regulated in cancer is not well understood and genes that modulate cancer autophagy are not fully defined. To gain more insights into autophagy regulation in cancer, we performed a large-scale RNA interference screen in K562 human chronic myeloid leukemia cells using monodansylcadaverine staining, an autophagy-detecting approach equivalent to immunoblotting of the autophagy marker LC3B or fluorescence microscopy of GFP-LC3B...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29433359/piperlongumine-restores-the-balance-of-autophagy-and-apoptosis-by-increasing-bcl2-phosphorylation-in-rotenone-induced-parkinson-disease-models
#6
Jia Liu, Weijin Liu, Yongquan Lu, Hao Tian, Chunli Duan, Lingling Lu, Ge Gao, Xia Wu, Xiaomin Wang, Hui Yang
Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease and is caused by genetics, environmental factors and aging, with few treatments currently available. Apoptosis and macroautophagy/autophagy play critical roles in PD pathogenesis; as such, modulating their balance is a potential treatment strategy. BCL2 (B cell leukemia/lymphoma 2) is a key molecule regulating this balance. Piperlongumine (PLG) is an alkaloid extracted from Piper longum L. that has anti-inflammatory and anticancer effects...
February 13, 2018: Autophagy
https://www.readbyqxmd.com/read/29409832/the-tumor-suppressor-cholesterol-metabolite-dendrogenin-a-is-a-new-class-of-lxr-modulator-activating-lethal-autophagy-in-cancers
#7
REVIEW
Marc Poirot, Sandrine Silvente-Poirot
Dendrogenin A (DDA) is a mammalian cholesterol metabolite recently identified that displays tumor suppressor properties. The discovery of DDA has revealed the existence in mammals of a new metabolic branch in the cholesterol pathway centered on 5,6α-epoxycholesterol and bridging cholesterol metabolism with histamine metabolism. Metabolic studies showed a drop in DDA levels in cancer cells and tumors compared to normal cells, suggesting a link between DDA metabolism deregulation and oncogenesis. Importantly, complementation of cancer cells with DDA induced 1) cancer cell re-differentiation, 2) blockade of 6-oxo-cholestan-3β,5α-diol (OCDO) production, an endogenous tumor promoter and 3) lethal autophagy in tumors...
January 31, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29382173/anti-cancerous-effect-of-inonotus-taiwanensis-polysaccharide-extract-on-human-acute-monocytic-leukemia-cells-through-ros-independent-intrinsic-mitochondrial-pathway
#8
Tsai-Ling Chao, Ting-Yin Wang, Chin-Huei Lee, Shuenn-Jiun Yiin, Chun-Te Ho, Sheng-Hua Wu, Huey-Ling You, Chi-Liang Chern
Acute leukemia is one of the commonly diagnosed neoplasms and causes human death. However, the treatment for acute leukemia is not yet satisfactory. Studies have shown that mushroom-derived polysaccharides display low toxicity and have been used clinically for cancer therapy. Therefore, we set out to evaluate the anti-cancerous efficacy of a water-soluble polysaccharide extract from Inonotus taiwanensis (WSPIS) on human acute monocytic leukemia THP-1 and U937 cell lines in vitro. Under our experimental conditions, WSPIS elicited dose-dependent growth retardation and induced apoptotic cell death...
January 29, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29377384/paris-saponin-vii-induces-cell-cycle-arrest-and-apoptosis-by-regulating-akt-mapk-pathway-and-inhibition-of-p-glycoprotein-in-k562-adr-cells
#9
Ting Yan, Gaosheng Hu, Anhua Wang, Xianduo Sun, Xiangyong Yu, Jingming Jia
Paris saponinVII (PSVII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii Maxim. We found that PSVII could inhibit the growth of adriamycin-resistant human leukemia cells (K562/ADR) in a dose-dependent manner. Furthermore, the molecular mechanism underlying the cytotoxicity and downregulation of P-glycoprotein (P-gp) expression by PSVII was clarified. PSVII significantly suppressed cell proliferation by cell cycle arrest in the G0/G1 phase, which was associated with an obvious decrease in cyclin B1/D1 and CDK2/4/6 protein expression...
January 29, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29376250/-progress-of-regulation-of-leukemia-stem-cells-of-chronic-myeloid-leukemia-by-autophagy
#10
Ling-Yan Zhu, Wei-Hong Ge, Yu-Qing Ge, Guang-Ji Zhang, Ru-Bin Cheng
Leukemia stem cells (LSC) that were found in chronic myeloid leukemia (CML) responsible for the abnormal proliferation with the potential of self-renewal and multi-directional differentiation are involved in the pathophysiological process for drug resistance and relapse of CML. Autophagy, a conservative lysosomal degradation process that mediates cell degradation and recycling process, plays crucial roles in maintaining the homeostasis and function of intracellular environment. Recent studies suggested that autophagy is involved in the regulation of LSC differentiation and also closely related to the chemo-sensitivity of CML...
December 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29374563/does-the-use-of-melatonin-overcome-drug-resistance-in-cancer-chemotherapy
#11
REVIEW
Mohammad Hossein Asghari, Emad Ghobadi, Milad Moloudizargari, Marjan Fallah, Mohammad Abdollahi
Our knowledge regarding the implications of melatonin in the therapy of numerous medical conditions, including cancer is constantly expanding. Melatonin can variably affect cancer pathology via targeting several key aspects of any neoplastic condition, including the very onset of carcinogenesis as well as tumor growth, differentiation, and dissemination. Numerous studies have examined the effects of melatonin in the context of various cancers reporting the enhanced efficacy of chemo/radiotherapy in combination with this compound...
January 25, 2018: Life Sciences
https://www.readbyqxmd.com/read/29368971/ligand-dependent-transcriptional-induction-of-lethal-autophagy-a-new-perspective-for-cancer-treatment
#12
Sandrine Silvente-Poirot, Gregory Ségala, Mathias C Poirot, Marc Poirot
Dendrogenin A (DDA) is a mammalian metabolite that displays anticancer and chemopreventive properties in mice. At the cancer cell level, DDA induces differentiation and death. We investigated herein the nature of DDA cytoxicity in cancer cells. We showed that DDA triggers biochemical and cellular features of macroautophagy/autophagy and that autophagy is cytotoxic. DDA induces both the accumulation of pro-lysosomal sterols and stimulates the expression of regulators of autophagy such as NR4A, LC3 and TFEB through binding to the liver X receptor (LXR), a ligand-dependent transcription factor consisting of 2 isoforms, NR1H2 and NR1H3...
January 25, 2018: Autophagy
https://www.readbyqxmd.com/read/29362482/arsenic-trioxide-promoting-etosis-in-acute-promyelocytic-leukemia-through-mtor-regulated-autophagy
#13
Tao Li, Ruishuang Ma, Yan Zhang, Hongdan Mo, Xiaoyan Yang, Shaoshan Hu, Lixiu Wang, Valerie A Novakovic, He Chen, Junjie Kou, Yayan Bi, Bo Yu, Shaohong Fang, Jinghua Wang, Jin Zhou, Jialan Shi
Despite the high efficacy and safety of arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL) and eradicating APL leukemia-initiating cells (LICs), the mechanism underlying its selective cytotoxicity remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, through autophagy. However, the role of ETosis in ATO-induced APL LIC eradication remains unclear. For this study, we evaluated the effects of ATO on ETosis and the contributions of drug-induced ETosis to APL LIC eradication...
January 23, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29346066/expression-of-autophagy-related-genes-in-chronic-lymphocytic-leukemia-is-associated-with-disease-course
#14
Yi-Lin Kong, Ying Huang, Jia-Zhu Wu, Xin Cao, Jin-Hua Liang, Yi Xia, Wei Wu, Lei Cao, Hua-Yuan Zhu, Li Wang, Lei Fan, Jian-Yong Li, Wei Xu
Autophagy leads cells to different fates in various cell types and under diverse contexts. Chronic lymphocytic leukemia (CLL), an incurable hematologic neoplasm, has highly variable course and its heterogeneity prompts interest in exploring autophagic trajectories in CLL. We detected the mRNA levels of two autophagy-related genes, BECN1 and ATG5, assessed the association between expression levels and clinical characteristics, and did survival analysis. One hundred and six patients with CLL and fifty healthy controls were enrolled in the present study...
January 3, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29334667/lithium-a-classic-drug-in-psychiatry-improves-nilotinib-mediated-antileukemic-effects
#15
Janaína Peixoto-da-Silva, Andrana K Calgarotto, Katiucha R Rocha, Caroline Palmeira-Dos-Santos, Soraya S Smaili, Gustavo J S Pereira, Fernando V Pericole, Adriana da Silva S Duarte, Sara T O Saad, Claudia Bincoletto
Although Tyrosine kinase inhibitors (TKIs) that target Bcr-Abl play a key role in Chronic Myeloid Leukemia (CML) therapy, they do not eradicate CML-initiating cells, which lead to the emergence of drug resistance. Here we used the lithium, a GSK-3 inhibitor, to attempt to potentiate the effects of nilotinib against leukemia cells. For this purpose, a K562 leukemia cell line and bone marrow cells from untreated Chronic Myeloid Leukemia (CML) patients, prior to any exposure to TKIs, were used as a model. Our results demonstrated that the combination of lithium + nilotinib (L + N) induced K562-cell death and cleaved caspase-3 when compared to lithium or nilotinib alone, accompanied by GSK-3β phosphorylation and Bcr-Abl oncoprotein levels reduction...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29332352/puerarin-leads-to-k562-cell-apoptosis-of-chronic-myelogenous-leukemia-via-induction-of-autophagy
#16
Da Gao, Zhen Xiao, Hui-Ping Li
PURPOSE: To study the effects of puerarin on the viability, apoptosis and autophagy of K562 cells of chronic myelogenous leukemia (CML), and to provide a basis for the study on antitumor mechanism of puerarin. METHODS: K562 cells of human CML were taken as the study material and puerarin was applied in different concentrations. The effect of puerarin on cell viability was detected via cholecystokinin-8 (CCK8) and lactate dehydrogenase (LDH). Flow cytometry and western blot (WB) were used to detect cell apoptosis, while Cyto-ID and WB were used to detect the cell autophagy level...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#17
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29295921/lymphocytes-eject-interferogenic-mitochondrial-dna-webs-in-response-to-cpg-and-non-cpg-oligodeoxynucleotides-of-class-c
#18
Björn Ingelsson, Daniel Söderberg, Tobias Strid, Anita Söderberg, Ann-Charlotte Bergh, Vesa Loitto, Kourosh Lotfi, Mårten Segelmark, Giannis Spyrou, Anders Rosén
Circulating mitochondrial DNA (mtDNA) is receiving increasing attention as a danger-associated molecular pattern in conditions such as autoimmunity, cancer, and trauma. We report here that human lymphocytes [B cells, T cells, natural killer (NK) cells], monocytes, and neutrophils derived from healthy blood donors, as well as B cells from chronic lymphocytic leukemia patients, rapidly eject mtDNA as web filament structures upon recognition of CpG and non-CpG oligodeoxynucleotides of class C. The release was quenched by ZnCl 2 , independent of cell death (apoptosis, necrosis, necroptosis, autophagy), and continued in the presence of TLR9 signaling inhibitors...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29290986/the-effect-of-the-jak2-inhibitor-tg101209-against-t-cell-acute-lymphoblastic-leukemia-t-all-is-mediated-by-inhibition-of-jak-stat-signaling-and-activation-of-the-crosstalk-between-apoptosis-and-autophagy-signaling
#19
Zhao Cheng, Yifang Yi, Sisi Xie, Haizhi Yu, Hongling Peng, Guangsen Zhang
Previous reports have shown that active JAK2 contributes to T cell acute lymphoblastic leukaemia (T-ALL) development and that JAK inhibitors may be a potential treatment for T-ALL. In the current study, the JAK2 inhibitor TG101209 was used to treat T-ALL cell lines and primary T-ALL cells. The effects of TG101209 on T-ALL cells were determined, and the signaling proteins related to cell growth, apoptosis and autophagy were analysed. The results indicated that TG101209 significantly inhibited T-ALL cell proliferation and induced cell apoptosis in a dose-dependent manner...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29259857/differences-of-basic-and-induced-autophagic-activity-between-k562-and-k562-adm-cells
#20
Feifei Wang, Jing Chen, Zhewen Zhang, Juan Yi, Minmin Yuan, Mingyan Wang, Na Zhang, Xuemin Qiu, Hulai Wei, Ling Wang
Patients with acute myeloid leukemia (AML) often have a poor prognosis due to drug resistance, which is regarded as a tough problem during the period of clinical therapeutics. It has been reported that autophagy, an important event in various cellular processes, plays a crucial role in mediating drug-resistance to cancer cells. Our study attempts to comparatively investigate the differences of basic and induced autophagic activity between drug-sensitive and multidrug-resistant AML cells. The level of basic autophagy in K562/ADM cells was higher than that in K562 cells, which could be characterized by more cytosolic contents-packaged autophagic vacuoles in K562/ADM cells when compared to that in K562 cells...
November 2017: Intractable & Rare Diseases Research
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