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https://www.readbyqxmd.com/read/28732387/the-micrornas-mir-200b-3p-and-mir-429-5p-target-the-limk1-cfl1-pathway-to-inhibit-growth-and-motility-of-breast-cancer-cells
#1
Dengfeng Li, Hong Wang, Hongming Song, Hui Xu, Bingkun Zhao, Chenyang Wu, Jiashu Hu, Tianqi Wu, Dan Xie, Junyong Zhao, Qiang Shen, Lin Fang
Triple-negative breast cancer (TNBC) has the worst prognosis of all subtypes of breast cancer (BC), with limited options for conventional therapy and no targeted therapies. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. In this study, we aimed to determine whether two members of the miR-200 family, miR-200b-3p and miR-429-5p, are involved in BC cell proliferation and motility and to elucidate their target genes and pathways. We performed a meta-analysis that reveals down-regulated expression of miR-200b-3p and miR-429-5p in BC tissues and cell lines, consistent with a lower expression of miR-200b-3p and miR-429-5p in MDA-MB-231 and HCC1937 cells than in MCF-7 and MCF-10 cells...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732355/checkpoint-kinase-1-inhibition-sensitises-transformed-cells-to-dihydroorotate-dehydrogenase-inhibition
#2
Stéphanie Arnould, Geneviève Rodier, Gisèle Matar, Charles Vincent, Nelly Pirot, Yoann Delorme, Charlène Berthet, Yoan Buscail, Jean Yohan Noël, Simon Lachambre, Marta Jarlier, Florence Bernex, Hélène Delpech, Pierre Olivier Vidalain, Yves L Janin, Charles Theillet, Claude Sardet
Reduction in nucleotide pools through the inhibition of mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) has been demonstrated to effectively reduce cancer cell proliferation and tumour growth. The current study sought to investigate whether this antiproliferative effect could be enhanced by combining Chk1 kinase inhibition. The pharmacological activity of DHODH inhibitor teriflunomide was more selective towards transformed mouse embryonic fibroblasts than their primary or immortalised counterparts, and this effect was amplified when cells were subsequently exposed to PF477736 Chk1 inhibitor...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28601509/olaparib-hydroxamic-acid-derivatives-as-dual-parp-and-hdac-inhibitors-for-cancer-therapy
#3
Zigao Yuan, Shaopeng Chen, Qinsheng Sun, Ning Wang, Dan Li, Shuangshuang Miao, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
Olaparib was the first PARP inhibitor approved by the FDA for patients with BRCA-mutated ovarian cancer. Recent studies have demonstrated enhanced anticancer effects of combination therapy consisting of olaparib and HDAC inhibitors. Herein, based on rational drug design strategy, hydroxamic acid derivatives of olaparib were constructed as dual PARP and HDAC inhibitors. These hybrid compounds showed potent inhibitory activities against PARP1/2 and HDAC1/6 with IC50 values in the nanomolar range. Furthermore, compound P1 exhibited broad-spectrum antiproliferative activities in selected human cancer cell lines...
May 31, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28599470/the-lipid-metabolism-gene-fto-influences-breast-cancer-cell-energy-metabolism-via-the-pi3k-akt-signaling-pathway
#4
Yazhuo Liu, Ruoyu Wang, Lichuan Zhang, Jianhua Li, Keli Lou, Bingyin Shi
The present study assessed the effect of the lipid metabolism, fat mass and the obesity-associated gene (FTO), on energy metabolism of breast cancer cells. The human breast cancer cell lines, MCF-7 and MDA-MB-231, and HCC1937 human breast cells were studied. Real-time PCR was used to measure the levels of FTO mRNA from breast cancer cells and normal breast cells. MDA-MB-231 cells were transfected with miFTO inhibitor or inhibitor control, and cells were assessed for levels of lactic acid, ATP, pyruvate kinase activity, and hexokinase activity assay using specific kits...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28560447/gro%C3%AE-overexpression-drives-cell-migration-and-invasion-in-triple-negative-breast-cancer-cells
#5
Kruttika Bhat, Marianna Sarkissyan, Yanyuan Wu, Jaydutt V Vadgama
Triple negative breast cancer (TNBC) is a subtype of highly aggressive breast cancer with poor prognosis. The main characteristic feature of TNBC is its lack of expression of ER, PR and HER2 receptors that are targets for treatments. Hence, it is imperative to identify novel therapeutic strategies to target TNBC. Our aim was to examine whether GROα is a specific marker for TNBC metastasis. For this we performed qPCR, ELISA, migration/invasion assays, western blotting, and siRNA transfections. Evaluation of baseline GROα expression in different breast cancer (BC) subtypes showed that it is significantly upregulated in breast tumor cells, specifically in TNBC cell line...
July 2017: Oncology Reports
https://www.readbyqxmd.com/read/28476158/melicope-ptelefolia-leaf-extracts-exhibit-antioxidant-activity-and-exert-anti-proliferative-effect-with-apoptosis-induction-on-four-different-cancer-cell-lines
#6
Mohammad Faujul Kabir, Johari Mohd Ali, Mitra Abolmaesoomi, Onn Haji Hashim
BACKGROUND: Melicope ptelefolia is a well-known herb in a number of Asian countries. It is often used as vegetable salad and traditional medicine to address various ailments. However, not many studies have been currently done to evaluate the medicinal benefits of M. ptelefolia (MP). The present study reports antioxidant, anti-proliferative, and apoptosis induction activities of MP leaf extracts. METHOD: Young MP leaves were dried, powdered and extracted sequentially using hexane (HX), ethyl acetate (EA), methanol (MeOH) and water (W)...
May 5, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28437471/mir-217-inhibits-triple-negative-breast-cancer-cell-growth-migration-and-invasion-through-targeting-klf5
#7
Wenhui Zhou, Fangfang Song, Qiuju Wu, Rong Liu, Lulu Wang, Cuicui Liu, You Peng, Shuqin Mao, Jing Feng, Ceshi Chen
Triple negative breast cancer (TNBC) is one of the most aggressive breast cancers without effective targeted therapies. Numerous studies have implied that KLF5 plays an important roles in TNBC. How is KLF5 regulated by microRNAs has not been well studied. Here, we demonstrated that miR-217 down-regulates the expression of KLF5 and KLF5's downstream target gene FGF-BP and Cyclin D1 in TNBC cell lines HCC1806 and HCC1937. Consequently, miR-217 suppresses TNBC cell growth, migration, and invasion. MiR-217 suppresses TNBC, at least partially, through down-regulating the KLF5 expression...
2017: PloS One
https://www.readbyqxmd.com/read/28322442/systems-analysis-of-dynamic-transcription-factor-activity-identifies-targets-for-treatment-in-olaparib-resistant-cancer-cells
#8
Joseph T Decker, Eric C Hobson, Yining Zhang, Seungjin Shin, Alexandra L Thomas, Jacqueline S Jeruss, Kelly B Arnold, Lonnie D Shea
The development of resistance to targeted therapeutics is a challenging issue for the treatment of cancer. Cancers that have mutations in BRCA, a DNA repair protein, have been treated with poly(ADP-ribose) polymerase (PARP) inhibitors, which target a second DNA repair mechanism with the aim of inducing synthetic lethality. While these inhibitors have shown promise clinically, the development of resistance can limit their effectiveness as a therapy. This study investigated mechanisms of resistance in BRCA-mutated cancer cells (HCC1937) to Olaparib (AZD2281) using TRACER, a technique for measuring dynamics of transcription factor (TF) activity in living cells...
September 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28052399/molecular-trail-for-the-anticancer-behavior-of-a-novel-copper-carbohydrazone-complex-in-brca1-mutated-breast-cancer
#9
Rakesh Sathish Nair, Manoj Easwaran Potti, Ratheeshkumar Thankappan, Sivakumar Krishnankutty Chandrika, M R Prathapachandra Kurup, Priya Srinivas
Novel chelated metal complexes were synthesized from carbohydrazones to thiocarbohydrazones using metal-based drug designing platforms and their combination effect with Pb, a naphthaquinone were analyzed for anticancer activity in breast cancer cell lines. A panel of BRCA1 wild-type and mutated breast cancer cells: MCF-7 (BRCA1(+) /ER(+) ), MDA-MB-231 (BRCA1(+) /ERα(-) ), HCC-1937 (BRCA1(-) /ERα(-) ), HCC1937/wt BRCA1, MX1 (BRCA1(-) /ERα(-) ), and MDA-MB-436 (BRCA1(-) /ERα(-) ) were screened for anti-cancer activity...
May 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27935867/the-bromodomain-inhibitor-otx015-mk-8628-exerts-anti-tumor-activity-in-triple-negative-breast-cancer-models-as-single-agent-and-in-combination-with-everolimus
#10
Ramiro Vázquez, María E Riveiro, Lucile Astorgues-Xerri, Elodie Odore, Keyvan Rezai, Eugenio Erba, Nicolò Panini, Andrea Rinaldi, Ivo Kwee, Luca Beltrame, Mohamed Bekradda, Esteban Cvitkovic, Francesco Bertoni, Roberta Frapolli, Maurizio D'Incalci
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subgroup of breast tumors clinically defined by the lack of estrogen, progesterone and HER2 receptors, limiting the use of the targeted therapies employed in other breast malignancies. Recent evidence indicates that c-MYC is a key driver of TNBC. The BET-bromodomain inhibitor OTX015 (MK-8628) has potent antiproliferative activity accompanied by c-MYC down-regulation in several tumor types, and has demonstrated synergism with the mTOR inhibitor everolimus in different models...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27917009/induced-expression-of-cancer-stem-cell-markers-aldh1a3-and-sox-2-in-hierarchical-reconstitution-of-apoptosis-resistant-human-breast-cancer-cells
#11
Karin Kashii-Magaribuchi, Rie Takeuchi, Yuko Haisa, Akemi Sakamoto, Aimi Itoh, Yuki Izawa, Miyuki Isa, Mayu Fukuzawa, Motonobu Murakami, Rei Takahashi
We established an experimental system that can induce p53-dependent apoptosis by doxycycline treatment to analyze characteristics of the apoptosis-resistant cancer cell subpopulation in the human breast cancer cell line HCC1937. Expression patterns of the stem cell markers, ALDH1A3 and Sox-2, the luminal differentiation marker, GATA3 and the proliferation index marker, Ki-67 were analyzed using immunostaining and fluorescence-activated cell sorting (FACS). After doxycycline treatment, the number of viable cells was gradually decreased over seven days in a time-dependent manner due to p53-induced apoptosis; however, the number of smaller-sized ALDH1A3(+) cells assessed by immunostaining increased sharply after 1 day of doxycycline treatment, suggesting their apoptosis-resistant nature...
November 1, 2016: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/27832772/calcitriol-stimulates-gene-expression-of-cathelicidin-antimicrobial-peptide-in-breast-cancer-cells-with-different-phenotype
#12
Janice García-Quiroz, Rocío García-Becerra, Nancy Santos-Martínez, Euclides Avila, Fernando Larrea, Lorenza Díaz
BACKGROUND: In normal and neoplastic cells, growth-promoting, proangiogenic, cytotoxic and pro-apoptotic effects have all been attributed to cathelicidin antimicrobial peptide (CAMP). Nevertheless, little is known about the factors regulating this peptide expression in breast cancer. Herein we asked if the well-known antineoplastic hormone calcitriol could differentially modulate CAMP gene expression in human breast cancer cells depending on the cell phenotype in terms of efficacy and potency...
November 10, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27811964/the-poly-adp-ribose-polymerase-inhibitor-veliparib-and-radiation-cause-significant-cell-line-dependent-metabolic-changes-in-breast-cancer-cells
#13
Vijesh J Bhute, Yan Ma, Xiaoping Bao, Sean P Palecek
Breast tumors are characterized into subtypes based on their surface marker expression, which affects their prognosis and treatment. Poly (ADP-ribose) polymerase (PARP) inhibitors have shown promising results in clinical trials, both as single agents and in combination with other chemotherapeutics, in several subtypes of breast cancer patients. Here, we used NMR-based metabolomics to probe cell line-specific effects of the PARP inhibitor Veliparib and radiation on metabolism in three breast cancer cell lines...
November 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27769200/selumetinib-suppresses-cell-proliferation-migration-and-trigger-apoptosis-g1-arrest-in-triple-negative-breast-cancer-cells
#14
Yan Zhou, Shuchen Lin, Kuo-Fu Tseng, Kun Han, Yaling Wang, Zhi-Hua Gan, Da-Liu Min, Hai-Yan Hu
BACKGROUND: Triple-negative breast cancer (TNBC) has aggressive progression with poor prognosis and ineffective treatments. Selumetinib is an allosteric, ATP-noncompetitive inhibitor of MEK1/2, which has benn known as effective antineoplastic drugs for several malignant tumors. We hypothesized that Selumetinib might be potential drug for TNBC and explore the mechanism. METHODS: After treated with Selumetinib, the viability and mobility of HCC1937 and MDA-MB-231 were detected by MTT, tunnel, wound-healing assay, transwell assay and FCM methods...
October 21, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27729799/the-role-of-semaphorin-4d-in-tumor-development-and-angiogenesis-in-human-breast-cancer
#15
Hongchao Jiang, Ceshi Chen, Qiangming Sun, Jing Wu, Lijuan Qiu, Change Gao, Weiqing Liu, Jun Yang, Nie Jun, Jian Dong
BACKGROUND: Semaphorin 4D (Sema4D) is highly expressed in certain types of tumors and functions in the regulation of tumor angiogenesis and growth. However, it is still not clear regarding the roles of Sema4D in breast cancer. This study was designed to explore the effects of Sema4D on proliferation, cell cycle progression, apoptosis, invasion, migration, tumor growth, and angiogenesis in breast cancer. MATERIALS AND METHODS: The expression level of Sema4D was investigated in MCF10A, 184A1, HCC1937, MDA-MB-468, MDA-MB-231, Hs578T, BT474, MCF-7, and T47D breast cancer cell lines by Western blotting analysis...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27477900/bard1-splice-variants-display-mislocalization-in-breast-cancer-cells-and-can-alter-the-apoptotic-response-to-cisplatin
#16
COMPARATIVE STUDY
Kamila A Marzec, Estefania Martino-Echarri, Irmgard Irminger-Finger, Beric R Henderson
We previously showed that BARD1 is a shuttling protein with pro-apoptotic activity in MCF-7 breast cancer cells. BARD1 is expressed as splice variant isoforms in breast cancer. Here we characterized YFP-tagged BARD1 splice variants (beta, omega, phi, ΔRIN, epsilon) for subcellular localization and apoptotic efficacy. We found that loss of nuclear localization (NLS) or export (NES) sequences influenced cellular distribution. The beta and omega variants (+NLS/-NES) shifted exclusively to the nucleus. In contrast, BARD1-epsilon (-NLS/+NES) was mostly cytoplasmic...
October 10, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27419628/glutamine-deprivation-plus-bptes-alters-etoposide-and-cisplatin-induced-apoptosis-in-triple-negative-breast-cancer-cells
#17
Lian Chen, Hengmin Cui, Jing Fang, Huidan Deng, Ping Kuang, Hongrui Guo, Xun Wang, Ling Zhao
Glutamine provides cancer cells with the energy required to synthesize macromolecules. Methods which block glutamine metabolism in treatment of breast cancer inhibit oncogenic transformation and tumor growth. We investigated whether inhibiting glutamine metabolism produces effects that are synergistic with those produced by drugs which damage DNA in triple-negative breast cancer cells. HCC1937 and BT-549 breast cancer cells were co-treated with either cisplatin or etoposide in combination with BPTES (a specific inhibitor of glutaminase 1) or exposure to a glutamine-free medium, and the cell proliferation and cell apoptosis were measured by flow cytometry, immunoblotting studies, and CCK-8 assays...
August 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27387452/a-new-oridonin-analog-suppresses-triple-negative-breast-cancer-cells-and-tumor-growth-via-the-induction-of-death-receptor-5
#18
Jing Wu, Ye Ding, Chuan-Huizhi Chen, Zhongmei Zhou, Chunyong Ding, Haiying Chen, Jia Zhou, Ceshi Chen
Triple-negative breast cancer (TNBC) remains the leading cause of death among women with breast cancer worldwide. Oridonin is a natural anti-cancer compound that is isolated from the traditional Chinese herb Rabdosia rubescens. However, the antitumor efficacies of oridonin in the treatments of TNBC and other cancers are far from ideal. In this study, we investigated a series of newly designed oridonin analogs in terms of their actions against HCC1806 and HCC1937 TNBC cell lines and identified CYD-6-28, which significantly inhibits cancer cell proliferation and induces G2/M-phase cell cycle arrest and apoptosis...
October 1, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27375368/parg-deficiency-is-neither-synthetic-lethal-with-brca1-nor-pten-deficiency
#19
Aurélia Noll, Giuditta Illuzzi, Jean-Christophe Amé, Françoise Dantzer, Valérie Schreiber
BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors have entered the clinics for their promising anticancer effect as adjuvant in chemo- and radiotherapy and as single agent on BRCA-mutated tumours. Poly(ADP-ribose) glycohydrolase (PARG) deficiency was also shown to potentiate the cytotoxicity of genotoxic agents and irradiation. The aim of this study is to investigate the effect of PARG deficiency on BRCA1- and/or PTEN-deficient tumour cells. METHODS: Since no PARG inhibitors are available for in vivo studies, PARG was depleted by siRNA in several cancer cell lines, proficient or deficient for BRCA1 and/or PTEN...
2016: Cancer Cell International
https://www.readbyqxmd.com/read/27364572/microrna-145-functions-as-a-tumor-suppressor-by-targeting-matrix-metalloproteinase-11-and-rab-gtpase-family-27a-in-triple-negative-breast-cancer
#20
L Tang, D Wei, F Yan
Although increasing evidence has documented that microRNA-145 (miR-145) acts as a tumor suppressor in breast cancer, its exact role in triple-negative breast cancer (TNBC) remains poorly defined. In this study, the expression of miR-145 in human TNBC cells and samples from 30 patients was analyzed by stem-loop real-time PCR. We found that miR-145 was significantly downregulated in TNBC tissues and cells. Upregulating miR-145 in HCC1937 cells dramatically suppressed cell proliferation and induced G1-phase arrest, whereas MDA-MB-231 cells did not show growth inhibition...
August 2016: Cancer Gene Therapy
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