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https://www.readbyqxmd.com/read/28633868/daidzein-stimulates-osteogenesis-facilitating-proliferation-differentiation-and-antiapoptosis-in-human-osteoblast-like-mg-63-cells-via-estrogen-receptor-dependent-mek-erk-and-pi3k-akt-activation
#1
Xin Jin, Jing Sun, Bo Yu, Yue Wang, Wei Jia Sun, Jing Yang, Su Hui Huang, Wen Li Xie
Daidzein, a natural soy isoflavone, has a structure similar to estradiol and exhibiting bone-sparing effects against osteoporosis. However, the molecular mechanisms of osteogenesis remain unclear. We hypothesized that daidzein stimulates osteogenesis through estrogen receptor (ER)-dependent signal pathways. To test this hypothesis, we investigated the effects of daidzein compared with 17β-estradiol on proliferation, differentiation, and cisplatin-induced apoptosis in human osteoblast-like MG-63 cells containing 2 ER isoforms...
June 2017: Nutrition Research
https://www.readbyqxmd.com/read/28627694/investigation-of-the-neuroprotective-effects-of-a-novel-synthetic-compound-via-the-mitochondrial-pathway
#2
Di Wang, Shuang Hu, Junrong Zhang, Qiuyue Li, Xinyu Liu, Yu Li
The present study aimed to investigate the neuroprotective effect of a novel synthetic compound (5zou) on differentiated PC12 cells against 6‑hydroxydopamine (6‑OHDA) and L‑glutamic acid (L‑Glu) neurotoxin‑induced cell injury and the potential mechanisms involved. 5zou is a 2, 2‑disubstituted 1,2‑dihydropyridine. PC12 cells were treated with 6‑OHDA and L‑Glu to establish neurotoxic cell models. MTT assay, DCFH‑DA staining, Fluo‑4‑AM staining, JC‑1 staining and western blotting were used to determine the changes in cell viability, intracellular reactive oxygen species concentration, Ca2+ influx, mitochondrial membrane potential and the protein expressions of B‑cell lymphoma‑2 (Bcl‑2) and B‑cell lymphoma‑extra large (Bcl‑xL)...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28623268/ascorbate-induces-apoptosis-in-melanoma-cells-by-suppressing-clusterin-expression
#3
Sushmita Mustafi, David W Sant, Zhao-Jun Liu, Gaofeng Wang
Pharmacological levels of ascorbate have long been suggested as a potential treatment of cancer. However, we observed that EC50 of ascorbate was at a similar level for cultured healthy melanocytes and melanoma cells, suggesting a limit of pharmacological ascorbate in treating cancer. Loss of 5-hydroxymethylcytosine (5 hmC) is an epigenetic hallmark of cancer and ascorbate promotes 5 hmC generation by serving as a cofactor for TET methylcytosine dioxygenases. Our previous work demonstrated that ascorbate treatment at physiological level (100 μM) increased 5 hmC content in melanoma cells toward the level of healthy melanocytes...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622054/down-regulation-of-liver-intestine-cadherin-enhances-noscapine-induced-apoptosis-in-human-colon-cancer-cells
#4
Xia Tian, Meng Liu, Qingxi Zhu, Jie Tan, Weijie Liu, Yanfen Wang, Wei Chen, Yanli Zou, Yishan Cai, Zheng Han, Xiaodong Huang
OBJECTIVES: Liver-intestine cadherin (CDH17) as a novel type of cadherin can significantly suppresses tumor growth in colon cancer cells. Noscapine is one of the most widely used antineoplastic agents in the treatment of solid tumor and haematological malignancies. The aim of the present study was to explore the signaling pathway of noscapine which induces apoptosis by blocking CDH17 gene in colon cancer SW480 cells. METHODS: Human colon cancer SW480 cells were transfected with CDH17 interference vector and treatment with 10 µmol/L noscapine...
June 16, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28618955/oridonin-synergizes-with-nutlin-3-in-osteosarcoma-cells-by-modulating-the-levels-of-multiple-bcl-2-family-proteins
#5
Xiao-Hui Wang, Shu-Feng Zhang, Jun-Tao Bao, Fu-Yun Liu
The small-molecule inhibitors of p53-murine double minute 2 interaction, such as Nutlin-3, are effective against cancers bearing wild-type p53. However, murine double minute 2 inhibitors often are unable to completely eliminate solid tumor cells. To address this issue, we investigated the anticancer effects of Nutlin-3 in combination with Oridonin in osteosarcoma cells. We found that Oridonin at sub-toxic concentrations synergistically enhanced Nutlin-3-mediated cell viability inhibition in wild-type p53 U2OS and SJSA-1, but not in p53-mutant MNNG/HOS and in null-p53 Saos-2 osteosarcoma cell lines...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28617432/bst2-confers-cisplatin-resistance-via-nf-%C3%AE%C2%BAb-signaling-in-nasopharyngeal-cancer
#6
Chun-Mei Kuang, Xiang Fu, Yi-Jun Hua, Wen-di Shuai, Zhi-Hua Ye, Yingchang Li, Qi-Hua Peng, Yi-Zhuo Li, Shuai Chen, Chao-Nan Qian, Wenlin Huang, Ran-Yi Liu
Concurrent/adjuvant cisplatin-based chemoradiotherapy is regarded as the standard of treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, patients who do not respond to cisplatin suffer, rather than benefit, from chemotherapy treatment. The goal of this study was to identify molecules involved in cisplatin resistance and to clarify their molecular mechanisms, which would help in the discovery of potential therapeutic targets and in developing a personalized and precise treatment approach for NPC patients...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28615521/ier3ip1-deficiency-leads-to-increased-%C3%AE-cell-death-and-decreased-%C3%AE-cell-proliferation
#7
Juan Sun, Decheng Ren
Mutations in the gene for Immediate Early Response 3 Interacting Protein 1 (IER3IP1) cause permanent neonatal diabetes mellitus in human. The mechanisms involved have not been determined and the role of IER3IP1 in β-cell survival has not been characterized. In order to determine if there is a molecular link between IER3IP1 deficiency and β-cell survival and proliferation, we knocked down Ier3ip1 gene expression in mouse MIN6 insulinoma cells. IER3IP1 suppression induced apoptotic cell death which was associated with an increase in Bim and a decrease in Bcl-xL...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28615297/disruption-of-aneuploidy-and-senescence-induced-by-aurora-inhibition-promotes-intrinsic-apoptosis-in-double-hit-or-double-expressor-diffuse-large-b-cell-lymphomas
#8
Daruka Mahadevan, Shariful Islam, Wenqing Qi, Carla Morales, Laurence Cooke, Catherine Spier, Eric Weterings
Double Hit (DH) or Double Expressor (DE) diffuse large B-cell lymphoma (DLBCL) are aggressive Non-Hodgkin's Lymphomas (NHLs) with translocations and/or over-expressions of MYC and BCL-2, that are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ~30%, while ~70% are aneuploid and senescent cells (AASCs), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway...
June 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28611196/atf3-repression-of-bcl-xl-determines-apoptotic-sensitivity-tohdac-inhibitors-across-tumour-types
#9
Anderly C Chüeh, Janson Wt Tse, Michael Dickinson, Paul Ioannidis, Laura Jenkins, Lars Tögel, BeeShin Tan, Ian Luk, Mercedes Dávalos-Salas, Rebecca Nightingale, Matthew R Thompson, Bryan Rg Williams, Guillaume Lessene, Erinna F Lee, Walter D Fairlie, Amardeep S Dhillon, John M Mariadason
Purpose: Histone deacetylase inhibitors (HDACi) are epigenome-targeting small molecules approved for the treatment of cutaneous T cell lymphoma and multiple myeloma. They have also demonstrated clinical activity in AML, non-small cell lung cancer and estrogen receptor-positive breast cancer, and trials are underway assessing their activity in combination regimens including immunotherpy.  However, there is currently no clear strategy to reliably predict HDACi sensitivity. <p>In colon cancer cells, apoptotic sensitivity to HDACi is associated with transcriptional induction of multiple immediate-early (IE) genes...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28611106/a-novel-combination-treatment-targeting-bcl-xl-and-mcl1-for-kras-braf-mutated-and-bcl2l1-amplified-colorectal-cancers
#10
Sung-Yup Cho, Jee Yun Han, Deukchae Na, Wonyoung Kang, Ahra Lee, Jooyoung Kim, Jieun Lee, Seoyeon Min, Jinjoo Kang, Jeesoo Chae, Jong-Il Kim, Hansoo Park, Won-Suk Lee, Charles Lee
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world, and exhibits heterogeneous characteristics in terms of genomic alterations, expression signature and drug responsiveness. Although there have been considerable efforts to classify this disease based on high-throughput sequencing techniques, targeted treatments for specific subgroups has been limited. KRAS and BRAF mutations are prevalent genetic alterations in CRCs, and patients with mutations in either of these genes have a worse prognosis and are resistant to anti-EGFR treatments...
June 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28607206/downregulation-of-mir-199a-5p-promotes-prostate-adeno-carcinoma-progression-through-loss-of-its-inhibition-of-hif-1%C3%AE
#11
Jinjing Zhong, Rui Huang, Zhengzheng Su, Mengni Zhang, Miao Xu, Jing Gong, Ni Chen, Hao Zeng, Xueqin Chen, Qiao Zhou
Hypoxia-inducible factor-1 alpha (HIF-1α) plays key roles in cell survival under both hypoxia and normoxia conditions. Regulation of HIF-1α is complex and involves numerous molecules and pathways, including post-transcriptional regulation by microRNAs (miRNAs). Although upregulation of HIF-1α has been shown to promote prostate adenocarcinoma (PCa) progression, the mechanism by which miRNAs modulate HIF-1α in prostate cancer has not been clarified. Here, we show that miR-199a-5p is underexpressed in prostate adenocarcinoma...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28598010/dleu1-contributes-to-ovarian-carcinoma-tumourigenesis-and-development-by-interacting-with-mir-490-3p-and-altering-cdk1-expression
#12
Li-Li Wang, Kai-Xuan Sun, Dan-Dan Wu, Yin-Ling Xiu, Xi Chen, Shuo Chen, Zhi-Hong Zong, Xiu-Bo Sang, Yao Liu, Yang Zhao
Recently, a large number of studies have focused on the important role of long non-coding RNAs (lncRNAs) in metabolism and development and have found that abnormal lncRNA expression is associated with the pathogenesis and development of many diseases. The lncRNA DLEU1 is involved in many solid tumours and haematological malignancies. However, its role in epithelial ovarian carcinoma (EOC) and the associated molecular mechanisms has not been reported. In this study, quantitative reverse transcription-PCR (qRT-PCR) demonstrated higher lncRNADLEU1 expression in EOC tissues than in normal tissues...
June 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28597245/protein-kinase-ck2-regulates-redox-homeostasis-through-nf-%C3%AE%C2%BAb-and-bcl-xl-in-cardiomyoblasts
#13
Susanne Schaefer, Barbara Guerra
Oxygen consumption is particularly elevated in cardiac cells as they are equipped with a large number of mitochondria and high levels of respiratory chain components. Consequently, production of reactive oxygen species (ROS) is tightly controlled as an imbalance in redox reactions can lead to irreversible cellular damage. siRNA-mediated down-regulation of protein kinase CK2 has been implicated in the accumulation of ROS in cells. The present study was undertaken in order to investigate the role of CK2 in redox homeostasis in cardiomyoblasts...
June 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28597042/cisplatin-induces-expression-of-drug-resistance-related-genes-through-c-jun-n-terminal-kinase-pathway-in-human-lung-cancer-cells
#14
Li Xu, Yingya Fu, Youlun Li, Xiaoli Han
PURPOSE: Change of multidrug resistance-related genes (e.g., lung resistance protein, LRP) and overexpression of anti-apoptotic genes (Bcl-2, Bcl-Xl, XIAP, Survivin) are responsible for cisplatin resistance. In our study, we investigated the mechanism by which cisplatin induces LRP, Bcl-2, Bcl-xL, XIAP, and Survivin expression in human lung adenocarcinoma A549 cells and human H446 small cell lung cancer cells at mRNA and protein levels. METHODS: In our study, cell proliferation was assessed with CCK-8 assays, and cell apoptosis was assessed with flow cytometric analysis and Annexin-V/PI staining...
June 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28596644/highlights-of-multiple-myeloma-at-the-annual-meeting-of-american-society-of-hematology-2016
#15
REVIEW
Nidhi Tandon, Shaji K Kumar
This review discusses the landmark studies in the field of multiple myeloma (MM) which were presented at American society of hematology annual meeting, 2016. There were contrary results from two large phase III trials (one from US and one from Europe) that evaluated the role of additional interventions like tandem autologous transplant (ASCT) and consolidation after induction therapy followed by ASCT in newly diagnosed MM (NDMM) patients, but there were critical differences between the two studies. Novel agents like carfilzomib and ixazomib proved to be of benefit when used as induction and post ASCT consolidation and maintenance in NDMM...
June 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28591707/identification-of-novel-small-molecule-beclin-1-mimetics-activating-autophagy
#16
Jia Yu, Lan Lan, Seth J Lewin, Steven A Rogers, Anuradha Roy, Xiaoqing Wu, Philip Gao, John Karanicolas, Jeffrey Aubé, Baiwang Sun, Liang Xu
Anti-apoptotic proteins Bcl-2 and Bcl-xL could block autophagy by binding to Beclin 1 protein, an essential inducer of autophagy. Compounds mimicking Beclin 1 might be able to disrupt Bcl-xL/2-Beclin 1 interaction, free out Beclin 1, and thus trigger autophagy. In order to identify small molecule Beclin 1 mimetics, a fluorescence polarization-based high-throughput screening of 50,316 compounds was carried out with a Z' score of 0.82 ± 0.05, and an outcome of 58 hits. After the structure analysis, three acridine analogues were unveiled and confirmed using the fluorescence polarization assay and the surface plasmon resonance assay...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28586716/design-synthesis-and-characterization-of-novel-quinacrine-analogs-that-preferentially-kill-cancer-over-non-cancer-cells-through-the-down-regulation-of-bcl-2-and-up-regulation-of-bax-and-bad
#17
V Raja Solomon, Danah Almnayan, Hoyun Lee
Both quinacrine, which contains a 9-aminoacridine scaffold, and thiazolidin-4-one are promising anticancer leads. In an attempt to develop effective and potentially safe anticancer agents, we synthesized 23 novel hybrid compounds by linking the main structural unit of the 9-aminoacridine ring with the thiazolidin-4-one ring system, followed by examination of their anticancer effects against three human breast tumor cell lines and matching non-cancer cells. Most of the hybrid compounds showed good activities, and many of them possessed the preferential killing property against cancer over non-cancer cells...
May 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28586114/a-phosphokinome-based-screen-uncovers-new-drug-synergies-for-cancer-driven-by-liver-specific-gain-of-non-oncogenic-rtks
#18
Yannan Fan, Maria Arechederra, Sylvie Richelme, Fabrice Daian, Chiara Novello, Julien Calderaro, Luca Di Tommaso, Guillaume Morcrette, Sandra Rebouissou, Matteo Donadon, Emanuela Morenghi, Jessica Zucman-Rossi, Massimo Roncalli, Rosanna Dono, Flavio Maina
Genetic mutations leading to oncogenic variants of receptor tyrosine kinases (RTKs) are frequent events during tumorigenesis; however, the cellular vulnerability to non-oncogenic RTK fluctuations has not been characterized. Here, we demonstrated genetically that liver subtle increases in wild-type Met RTK levels are sufficient for spontaneous tumors in mice (Alb-R26(Met) ), conceptually illustrating how the shift from physiological to pathological conditions results from slight perturbations in signaling dosage...
June 6, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28586007/apg-1252-12a-induces-mitochondria-dependent-apoptosis-through-inhibiting-the-antiapoptotic-proteins-bcl-2-bcl-xl-in-hl-60-cells
#19
Jing Wang, Dajun Yang, Qiuyun Luo, Miaozhen Qiu, Lin Zhang, Baoxia Li, Haibo Chen, Hanjie Yi, Xianglei Yan, Shuxia Li, Jian Sun
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Despite improved remission rates, current treatment regimens for AML are often associated with a very poor prognosis and adverse effects, necessitating more effective and safer agents. B-cell leukemia/lymphoma 2 (Bcl-2) family proteins regulate apoptotic pathway that can be targeted with small molecule inhibitors. APG-1252-12A is a Bcl-2 homology (BH)-3 mimetic that specifically binds to Bcl-2 and Bcl-xl, which has shown efficacy in some Bcl-2 dependent hematological cancers...
June 6, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28583549/reduction-of-slit-diaphragm-associated-molecules-by-sirolimus-is-it-enough-to-induce-proteinuria
#20
B S Kim, J G Lee, Y Cho, S H Song, K H Huh, M S Kim, Y S Kim
Sirolimus (SRL), a mammalian target of rapamycin inhibitor, is widely used in transplantation, but the mechanisms whereby it induces adverse effects, such as proteinuria and edema, remain unclear. To determine whether isolated SRL induces proteinuria or not, the authors intraperitoneally injected C57BL/6 mice with different doses of SRL (0 mg/[kg·d], 3 mg/[kg·d], 10 mg/[kg·d], or 30 mg/[kg·d]) for 24 days. Urinary albumin excretion was then quantified using a double-sandwich enzyme-linked immunosorbent assay, and serum creatinine levels were measured using a single dry-film chemistry auto-analyzer...
June 2017: Transplantation Proceedings
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