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https://www.readbyqxmd.com/read/28920958/the-n-6-methyladenosine-m-6-a-forming-enzyme-mettl3-controls-myeloid-differentiation-of-normal-hematopoietic-and-leukemia-cells
#1
Ly P Vu, Brian F Pickering, Yuanming Cheng, Sara Zaccara, Diu Nguyen, Gerard Minuesa, Timothy Chou, Arthur Chow, Yogesh Saletore, Matthew MacKay, Jessica Schulman, Christopher Famulare, Minal Patel, Virginia M Klimek, Francine E Garrett-Bakelman, Ari Melnick, Martin Carroll, Christopher E Mason, Samie R Jaffrey, Michael G Kharas
N(6)-methyladenosine (m(6)A) is an abundant nucleotide modification in mRNA that is required for the differentiation of mouse embryonic stem cells. However, it remains unknown whether the m(6)A modification controls the differentiation of normal and/or malignant myeloid hematopoietic cells. Here we show that shRNA-mediated depletion of the m(6)A-forming enzyme METTL3 in human hematopoietic stem/progenitor cells (HSPCs) promotes cell differentiation, coupled with reduced cell proliferation. Conversely, overexpression of wild-type METTL3, but not of a catalytically inactive form of METTL3, inhibits cell differentiation and increases cell growth...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28915591/eugenol-alleviated-breast-precancerous-lesions-through-her2-pi3k-akt-pathway-induced-cell-apoptosis-and-s-phase-arrest
#2
Min Ma, Yi Ma, Gui-Juan Zhang, Rui Liao, Xue-Feng Jiang, Xian-Xin Yan, Feng-Jie Bie, Xiao-Bo Li, Yan-Hong Lv
Eugenol can be separated from the oil extract of clove bud, and has many pharmacological functions such as anticancer and transdermal absorption. HER2/PI3K-AKT is a key signaling pathway in the development of breast cancer. In this study, 80 μM eugenol could significantly inhibit the proliferation of HER-2 positive MCF-10AT cells and the inhibition rate was up to 32.8%, but had no obvious inhibitory effect on MCF-7 and MCF-10A cells with HER2 weak expression. Eugenol also significantly induced human breast precancerous lesion MCF-10AT cell apoptosis and cell cycle S-phase arrest, but the biological effects nearly disappeared after HER2 over-expression through transfecting pcDNA3...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28899512/nepeta-deflersiana-attenuates-isoproterenol-induced-myocardial-injuries-in-rats-possible-involvement-of-oxidative-stress-apoptosis-inflammation-through-nuclear-factor-nf-%C3%AE%C2%BAb-downregulation
#3
Areej Mohammad Al-Taweel, Mohammad Raish, Shagufta Perveen, Ghada Ahmed Fawzy, Ajaz Ahmad, Mushtaq Ahmad Ansari, Shahid Mudassar, Majid Ahmad Ganaie
BACKGROUND: Nepeta deflersiana (Lamiaceae) is a perennial herb used in the Saudi and Yemeni folk medicine as an anti-inflammatory, carminative, and antirheumatic agent. PURPOSE: This study explores the phytochemistry of the plant and the cardioprotective effect of N. deflersiana ethanolic extract (NDEE) against isoproterenol (ISP)-induced myocardial injury in rats. DESIGN/METHODS: Cardiac function, serum cardiac enzymes, myocardial antioxidants, inflammatory, and apoptotic biomarkers, and histopathological parameters were studied in ISP-injured Wistar rat heart tissues...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28892788/triptolide-suppresses-growth-and-hormone-secretion-in-murine-pituitary-corticotroph-tumor-cells-via-nf-kappab-signaling-pathway
#4
Ran Li, Zhuo Zhang, Junwen Wang, Yiming Huang, Wei Sun, Ruifan Xie, Feng Hu, Ting Lei
Triptolide is a principal diterpene triepoxide from the Chinese medical plant Tripterygium wilfordii Hook. f., whose extracts have been utilized in dealing with diverse diseases in traditional Chinese medicine for centuries. Recently, the antitumor effect of triptolide has been found in several pre-clinical neoplasm models, but its effect on pituitary corticotroph adenomas has not been investigated so far. In this study, we are aiming to figure out the antitumor effect of triptolide and address the underlying molecular mechanism in AtT20 murine corticotroph cell line...
September 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28886883/alternative-splicing-of-telomerase-catalytic-subunit-htert-generated-by-apoptotic-endonuclease-endog-induces-human-cd4-t-cell-death
#5
Dmitry D Zhdanov, Daria A Vasina, Vladimir A Grachev, Elena V Orlova, Valentina S Orlova, Marina V Pokrovskaya, Svetlana S Alexandrova, Nikolai N Sokolov
Telomerase activity is regulated by alternative splicing of its catalytic subunit human Telomerase Reverse Transcriptase (hTERT) mRNA. Induction of a non-active spliced hTERT leads to inhibition of telomerase activity. However, very little is known about the mechanism of hTERT mRNA alternative splicing. The aim of this study was to determine the role of the apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. A strong correlation was identified between EndoG expression levels and hTERT splice variants in human CD4(+) and CD8(+) T lymphocytes...
September 1, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28875330/liposomes-co-loaded-with-6-phosphofructo-2-kinase-fructose-2-6-biphosphatase-3-pfkfb3-shrna-plasmid-and-docetaxel-for-the-treatment-of-non-small-cell-lung-cancer
#6
Nusrat Chowdhury, Imran Vhora, Ketan Patel, Ravi Doddapaneni, Arindam Mondal, Mandip Singh
PURPOSE: Non-small cell lung cancer is the leading cause of cancer related deaths globally. Considering the side effects and diminishing chemosensitivity to chemotherapy, novel treatment approaches are sought. Hence, we aim to develop a liposomal co-delivery system of pDNA expressing shRNA against PFKFB3 (pshPFKFB3) and docetaxel (DTX). METHODS: Cationic DTX liposomes complexed with pshPFKFB3 (PSH-DL) were developed. In vitro cell line studies were performed to evaluate transfection, PFKFB3 mRNA silencing, cytotoxicity, pGP inhibition, and protein markers expression...
September 5, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28865123/kaempferol-increases-apoptosis-in-human-acute-promyelocytic-leukemia-cells-and-inhibits-multidrug-resistance-genes
#7
Maliheh Moradzadeh, Alijan Tabarraei, Hamid Reza Sadeghnia, Ahmad Ghorbani, Ashraf Mohamadkhani, Saiedeh Erfanian, Amirhossein Sahebkar
Acute promyelocytic leukemia (APL) is one of the most life-threatening hematological malignancies. Defects in the cell growth and apoptotic pathways are responsible for both disease pathogenesis and treatment resistance. Therefore, pro-apoptotic agents are potential candidates for APL treatment. Kaempferol is a flavonoid with antioxidant and anti-tumor properties. This study was designed to investigate the cytotoxic, pro-apoptotic and differentiation-inducing effects of kaempferol on HL-60 and NB4 leukemia cells...
September 2, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28858737/ginkgo-biloba-l-leaf-extract-offers-multiple-mechanisms-in-bridling-n-methylnitrosourea-mediated-experimental-colorectal-cancer
#8
Hanaa H Ahmed, Hanan S El-Abhar, Elsayed Abdul Khalik Hassanin, Noha F Abdelkader, Mohamed B Shalaby
In Egypt, colorectal cancer (CRC) is the 6th cancer in both gender and CRC rates are high in subjects under 40 years of age. This study goaled to determine the development of CRC using relevant biochemical markers and to elucidate the potent mechanism of Ginkgo biloba L. leaf extract in retrogression of experimental CRC. Adult male Sprague-Dawley rats were administered N-methylnitrosourea (N-MNU; 2mg in 0.5ml water/rat) intrarectally thrice a week for five weeks to induce CRC, followed by treatment with either 5-fluorouracil (5-FU; 12...
August 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28855652/xwl-1-48-exerts-antitumor-activity-via-targeting-topoisomerase-ii-and-enhancing-degradation-of-mdm2-in-human-hepatocellular-carcinoma
#9
Yajie Wang, Hua Sun, Zhiyan Xiao, Dan Zhang, Xiuqi Bao, Ning Wei
A novel podophyllotoxin derivative, XWL-1-48, was synthesized as an oral topoisomerase II inhibitor. kDNA decatenation assay indicated that XWL-1-48 significantly inhibited topoisomerase II activity in a concentration-dependent manner. Moreover, the cytotoxicity of XWL-1-48 is more potent than its congener GL331 and the IC50 values are from 0.34 ± 0.21 to 3.54 ± 0.54 µM in 10 cancer cell lines including KBV200 cells with P-gp overexpression. Noticeably, XWL-1-48 exerted potent antitumor activity in in vitro and in vivo human hepatocellular carcinoma (HCC) model...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855578/hur-targeted-small-molecule-inhibitor-exhibits-cytotoxicity-towards-human-lung-cancer-cells
#10
Ranganayaki Muralidharan, Meghna Mehta, Rebaz Ahmed, Sudeshna Roy, Liang Xu, Jeffrey Aubé, Allshine Chen, Yan Daniel Zhao, Terence Herman, Rajagopal Ramesh, Anupama Munshi
Human antigen (Hu) R is an RNA-binding protein whose overexpression in human cancer correlates with aggressive disease, drug resistance, and poor prognosis. HuR inhibition has profound anticancer activity. Pharmacologic inhibitors can overcome the limitations of genetic inhibition. In this study, we examined the antitumor activity of CMLD-2, a small-molecule inhibitor directed against HuR, using non-small cell lung cancer (NSCLC) as a model. CMLD-2 efficacy was tested in vitro using H1299, A549, HCC827, and H1975 NSCLC cells and MRC-9 and CCD-16 normal human fibroblasts...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28852199/mutant-jak3-phosphoproteomic-profiling-predicts-synergism-between-jak3-inhibitors-and-mek-bcl2-inhibitors-for-the-treatment-of-t-cell-acute-lymphoblastic-leukemia
#11
S Degryse, C E de Bock, S Demeyer, I Govaerts, S Bornschein, D Verbeke, K Jacobs, S Binos, D A Skerrett-Byrne, H C Murray, N M Verrills, P Van Vlierberghe, J Cools, M D Dun
Mutations in the interleukin-7 receptor (IL7R) or the JAK3 kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here, we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells. Signaling pathways regulated by JAK3 mutants were assessed following acute inhibition of JAK1/JAK3 using the JAK kinase inhibitors ruxolitinib or tofacitinib...
August 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28851813/the-influential-role-of-bcl2-family-members-in-synovial-sarcomagenesis
#12
Jared J Barrott, Ju-Fen Zhu, Kyllie Smith-Fry, Asia M Susko, Dakota Nollner, Lance Burrell, Amir Pozner, Mario R Capecchi, Jeffrey T Yap, Lisa A Cannon-Albright, Xingming Deng, Kevin B Jones
Synovial sarcomas are deadly soft-tissue malignancies associated with t(X;18) balanced chromosomal translocations. Expression of the apoptotic regulator BCL2 is prominent in synovial sarcomas and has prompted the hypothesis that synovial sarcomagenesis may depend on it. Herein, it is demonstrated that Bcl2 overexpression enhances synovial sarcomagenesis in an animal model. Further, we determined increased familial clustering of human synovial sarcoma patients with victims of other BCL2-associated malignancies in the Utah Population Database...
August 29, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28851623/diethylcarbamazine-a-potential-treatment-drug-for-pulmonary-hypertension
#13
Edlene Lima Ribeiro, Ingrid Tavares Fragoso, Fabiana Oliveira Dos Santos Gomes, Amanda Costa Oliveira, Amanda Karoline Soares E Silva, Patrícia Martins E Silva, Bianca Torres Ciambarella, Isalira Peroba Rezende Ramos, Christina Alves Peixoto
The present study demonstrated the potential effects of diethylcarbamazine (DEC) on monocrotaline (MCT)-induced pulmonary hypertension. MCT solution (600mg/kg) was administered once per week, and 50mg/kg body weight of DEC for 28days. Three C57Bl/6 male mice groups (n=10) were studied: Control; MCT28, and MCT28/DEC. Echocardiography analysis was performed and lung tissues were collected for light microscopy (hematoxylin-eosin and Masson's trichrome staining), immunohistochemistry (αSMA, FADD, caspase 8, caspase 3, BAX, BCL2, cytochrome C and caspase 9) western blot (FADD, caspase 8, caspase 3, BAX, BCL2, cytochrome C and caspase 9) and qRt-PCR (COL-1α and αSMA)...
August 26, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28842171/colistin-induced-autophagy-and-apoptosis-involves-the-jnk-bcl2-bax-signaling-pathway-and-jnk-p53-ros-positive-feedback-loop-in-pc-12-cells
#14
Ziyin Lu, Yusong Miao, Ishfaq Muhammad, Erjie Tian, Wanjun Hu, Jian Wang, Bo Wang, Rui Li, Jichang Li
Our recent study demonstrated neurotoxicity of colistin-induced autophagy and apoptosis in PC-12 cells, and that autophagy reached peak level at 12 h. In this study, we scrutinized the role of JNK in colistin-induced neurotoxicity and demonstrated the relationship among JNK, p53 and ROS in colistin treated PC-12 cells. Colistin-induced autophagy and apoptosis by JNK inhibition/activation were examined by western blotting, electron microscopy, and immunofluorescence/fluorescence microscopy. The results indicated that colistin induced JNK activation reached peak level at 12 h, while the highest levels of p-Bcl2/Bcl2 were observed at 12 h and Bax/Bcl2 significantly increased in a time-dependent manner...
August 24, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28840369/novel-histone-deacetylase-8-selective-inhibitor-1-3-4-oxadiazole-alanine-hybrid-induces-apoptosis-in-breast-cancer-cells
#15
Vijaya Rao Pidugu, Nagendra Sastry Yarla, Anupam Bishayee, Arunasree M Kalle, Alapati Krishna Satya
Identification of isoform-specific histone deacetylase inhibitors (HDACi) is a significant advantage to overcome the adverse side effects of pan-HDACi for the treatment of various diseases, including cancer. We have designed, and synthesized novel 1,3,4 oxadiazole with glycine/alanine hybrids as HDAC8-specific inhibitors and preliminary evaluation has indicated that 1,3,4 oxadiazole with alanine hybrid [(R)-2-amino-N-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)propanamide (10b)] to be a potent HDAC8 inhibitor. In the present study, the in vitro efficacy of the molecule in inhibiting the cancer cell proliferation and the underlying molecular mechanism was studied...
August 24, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28827731/microrna-7641-is-a-regulator-of-ribosomal-proteins-and-a-promising-targeting-factor-to-improve-the-efficacy-of-cancer-therapy
#16
Abu Musa Md Talimur Reza, Yun-Jung Choi, Yu-Guo Yuan, Joydeep Das, Hideyo Yasuda, Jin-Hoi Kim
Many diseases, including myocardial infarction, autoimmune disease, viral diseases, neurodegenerative diseases, and cancers, are frequently diagnosed with aberrant expression of microRNAs (miRNAs) and their allied pathways. This indicates the crucial role of miRNAs in maintaining biological and physiological processes. miR-7641 is a miRNA whose role in disease has not been fully investigated. In the present study, we investigated the expression pattern of miR-7641 and its target genes in different cancer cells, as well as in clinical cancer patients...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28826362/mir-3074-5p-promotes-the-apoptosis-but-inhibits-the-invasiveness-of-human-extravillous-trophoblast-derived-htr8-svneo-cells-in-vitro
#17
Yan Gu, Yan Shi, Qian Yang, Wen-Wen Gu, Ya-Ping He, Hua-Jun Zheng, Xuan Zhang, Jian-Mei Wang, Jian Wang
OBJECTIVE: The objective of this study was to observe the effects of the overexpression of miR-3074-5p in human trophoblast cells in vitro. DESIGN: Experimental in vitro study in HTR8/SVneo cells. METHODS: HTR8/SVneo cells were transfected with miR-3074-5p mimic. The cell apoptosis and invasion were measured via flow cytometry and transwell assay, respectively. The expression levels of P53, Cyclin Dependent Kinase Inhibitor 1B (P27), BCL-2, BCL2 associated X (BAX), and BCL2 like 14 (BCL-G) in HTR8/SVneo cells were determined by Western blot...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28817115/administration-of-follicle-stimulating-hormone-induces-autophagy-via-upregulation-of-hif-1%C3%AE-in-mouse-granulosa-cells
#18
Jilong Zhou, Wang Yao, Chengyu Li, Wangjun Wu, Qifa Li, Honglin Liu
Recent studies reported the important role of autophagy in follicular development. However, the underlying molecular mechanisms remain elusive. In this study, we investigated the effect of follicle-stimulating hormone (FSH) on mouse granulosa cells (MGCs). Results indicated that autophagy was induced by FSH, which is known to be the dominant hormone regulating follicular development and granulosa cell (GC) proliferation. The activation of mammalian target of rapamycin (mTOR), a master regulator of autophagy, was inhibited during the process of MGC autophagy...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28812970/indole-3-carbinol-induces-g1-cell-cycle-arrest-and-apoptosis-through-aryl-hydrocarbon-receptor-in-thp-1-monocytic-cell-line
#19
Saeed Mohammadi, Fakhri Sadat Seyedhosseini, Nasser Behnampour, Yaghoub Yazdani
OBJECTIVES: The role of aryl hydrocarbon receptor (AhR) in carcinogenesis has been studied recently. Indole-3-carbinol (I3C) is an AhR agonist and a potential anticancer agent. Here, we investigated the effects of I3C on cell cycle progression and apoptosis through activation of AhR on THP-1 acute myeloid leukemia (AML) cell line. METHODS: MTT viability assay was used to measure the cytotoxic effects of I3C on THP-1 cells. Apoptosis and cell cycle assays were investigated using flow cytometry...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28805353/the-role-of-melatonin-receptor-mtnr1a-in-the-action-of-melatonin-on-bovine-granulosa-cells
#20
Shu-Juan Wang, Wen-Ju Liu, Li-Ke Wang, Xun-Sheng Pang, Li-Guo Yang
Granulosa cells (GCs) play an important role in ovarian follicle growth, development, and follicular atresia. In the present study, we investigated the effects of Melatonin on bovine GCs, and asked if MTNR1A was involved in their response to this indole hormone. Our results indicated that Melatonin inhibited GC apoptosis by up-regulating the expression of BCL2, BCL-XL, GPX4, and SOD1, and down-regulating the expression of BAX, CASP3, and TP53. Moreover, Melatonin modulated bovine GC function by decreasing the expression of INHA, INHBB, FSHR, and TGFBR3, and the abundance of Inhibin β and Activin B, while increasing the expression of LHR, INHBA, and secretion of progesterone by GCs...
August 14, 2017: Molecular Reproduction and Development
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