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Author (up) Chen, C.; Chan, H.M.; Kubow, S. file  url
  Title Kefir extracts suppress in vitro proliferation of estrogen-dependent human breast cancer cells but not normal mammary epithelial cells Type Journal Article
  Year 2007 Publication Journal of Medicinal Food Abbreviated Journal J Med Food  
  Volume 10 Issue 3 Pages 416-422  
  Keywords Animals; Breast/cytology; Breast Neoplasms/*pathology; Cell Division/*drug effects; Cell Line, Tumor; Cultured Milk Products/*chemistry; Epithelial Cells/drug effects; Fermentation; Humans; Milk/chemistry; Milk Proteins/analysis; Peptides/analysis; Yogurt/analysis  
  Abstract Anti-tumorigenic effects have been demonstrated in animal studies from the intake of kefir, a traditional fermented milk product believed to originate from the Caucasian mountains of Russia. In the present study, the antiproliferative effects of extracts of kefir, yogurt, and pasteurized cow's milk on human mammary cancer cells (MCF-7) and normal human mammary epithelial cells (HMECs) was investigated at doses of 0.31%, 0.63%, 1.25%, 2.5%, 5%, and 10% (vol/vol). After 6 days of culture, extracts of kefir-fermented milk depressed MCF-7 cell growth in a dose-dependent manner, showing 29% inhibition of proliferation at a concentration as low as 0.63%, whereas yogurt extracts began to show dose-dependent antiproliferative effects only at the 2.5% dose. Moreover, at the 2.5% dose, kefir extracts decreased the MCF-7 cell numbers by 56%, while yogurt extracts decreased MCF-7 cell proliferation by only 14%. No antiproliferative effects of kefir extracts were observed in the HMECs, while the yogurt extracts exerted antiproliferative effects on HMECs at the 5% and 10% doses. Unfermented milk extracts stimulated proliferation of MCF-7 cells and HMECs at concentrations above 0.31%. Peptide content and capillary electrophoresis analyses showed that kefir-mediated milk fermentation led to an increase in peptide concentrations and a change in peptide profiles relative to milk or yogurt. The present findings suggest that kefir extracts contain constituents that specifically inhibit the growth of human breast cancer cells, which might eventually be useful in the prevention or treatment of breast cancer.  
  Call Number Serial 1055  
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Author (up) Henkenius, K.; Greene, B.H.; Barckhausen, C.; Hartmann, R.; Marken, M.; Kaiser, T.; Rehberger, M.; Metzelder, S.K.; Parak, W.J.; Neubauer, A.; Brendel, C.; Mack, E. file  url
  Title Maintenance of cellular respiration indicates drug resistance in acute myeloid leukemia Type Journal Article
  Year 2017 Publication Leukemia Research Abbreviated Journal Leuk Res  
  Volume 62 Issue Pages 56-63  
  Keywords Cell Line, Tumor; Cell Respiration/*physiology; Drug Resistance, Neoplasm/*physiology; Glycolysis/drug effects/physiology; Humans; Leukemia, Myeloid, Acute/*metabolism; Oxidative Phosphorylation/drug effects; Aml; Drug resistance; Mitochondrial membrane potential; Respiration  
  Abstract Primary resistance to induction therapy is an unsolved clinical problem in acute myeloid leukemia (AML). Here we investigated drug resistance in AML at the level of cellular metabolism in order to identify early predictors of therapeutic response. Using extracellular flux analysis, we compared metabolic drug responses in AML cell lines sensitive or resistant to cytarabine or sorafenib after 24h of drug treatment to a small cell lung cancer (SCLC) cell line exposed to etoposide. Only drug-resistant AML cells maintained oxidative metabolism upon drug exposure while SCLC cells displayed an overall metabolic shift towards glycolysis, i.e. a Warburg effect to escape drug toxicity. Moreover, primary AML blasts displayed very low glycolytic activity, while oxygen consumption was readily detectable, indicating an essential role of oxidative pathways in the bioenergetics of AML blasts. In line with these observations, analysis of the mitochondrial membrane potential using tetramethylrhodamine ethyl ester staining and flow cytometry allowed for clear discrimination between drug sensitive and resistant AML cell line clones and primary blasts after 24h of treatment with cytarabine or sorafenib. Our data reveal a distinct metabolic phenotype of resistant AML cells and suggest that disrupting oxidative metabolism rather than glycolysis may enhance the cytotoxic effects of chemotherapy in AML.  
  Call Number Serial 2125  
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Author (up) Kang, Y.H.; Lee, K.-A.; Ryu, C.J.; Lee, H.-G.; Lim, J.-S.; Park, S.N.; Paik, S.-G.; Yoon, D.-Y. file  url
doi  openurl
  Title Mitomycin C induces apoptosis via Fas/FasL dependent pathway and suppression of IL-18 in cervical carcinoma cells Type Journal Article
  Year 2006 Publication Cancer Letters Abbreviated Journal Cancer Lett  
  Volume 237 Issue 1 Pages 33-44  
  Keywords Antibiotics, Antineoplastic/*pharmacology; Antigens, CD95; Antineoplastic Agents/*pharmacology; *Apoptosis; Caspase 3; Caspase 8; Caspases/metabolism; Cell Line, Tumor; Cell Survival/drug effects; Cisplatin/pharmacology; Fas Ligand Protein; Female; Humans; I-kappa B Proteins/antagonists & inhibitors/metabolism; Interleukin-18/antagonists & inhibitors/*metabolism; Membrane Glycoproteins/*metabolism; Mitomycin/*pharmacology; Oncogene Proteins, Viral/genetics; Receptors, Tumor Necrosis Factor/*metabolism; Repressor Proteins/genetics; Signal Transduction/*drug effects; Transfection; Tumor Necrosis Factors/*metabolism; Uterine Cervical Neoplasms  
  Abstract Mitomycin C (MMC) is used fairly widely as an anticancer drug, as it possesses mechanisms of action which are preferable to other chemotherapeutic compounds, including cisplatin, docetaxel, and lovastatin. In the previous study, we established the RSV-luc promoter analysis system, which is used to screen drugs against cervical carcinomas caused by HPV infection. We then demonstrated the repression of HPV E6-activated RSV promoter activity by anticancer agents such as carboplatin (CA), cisplatin (CIS), and MMC. In these studies, we focused on the investigation of apoptotic mechanisms in MMC-treated cervical carcinoma cell lines, most notably SiHa/pRSV-luc (KCTC 0427BP) and SiHa. DNA fragmentation assays and TUNEL staining revealed that MMC and CIS, but not CA, resulted in apoptosis. MMC treatment induced a reduction in the expressions of the E6 oncogene and IL-18, in a p53-independent manner. MMC also increased FasL expression and induced the processing of caspases-8 and -3. Our results indicated that MMC induced apoptosis in SiHa/pRSV-luc and SiHa cells via caspase-8 and -3 processing, in a Fas/FasL-dependent manner. MMC also suppressed the expression of IL-18 in the same cells. MMC also down-regulated IkappaB expression, and up-regulated p65 expression. These results suggest that MMC induces apoptosis, not only through caspase-8 and -3 dependent Fas/FasL pathway, but also via the regulation of NF-kappaB activity and IL-18 expression.  
  Call Number Serial 198  
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Author (up) Marimani, M.D.; Ely, A.; Buff, M.C.R.; Bernhardt, S.; Engels, J.W.; Arbuthnot, P. file  url
  Title Inhibition of hepatitis B virus replication in cultured cells and in vivo using 2'-O-guanidinopropyl modified siRNAs Type Journal Article
  Year 2013 Publication Bioorganic & Medicinal Chemistry Abbreviated Journal Bioorg Med Chem  
  Volume 21 Issue 20 Pages 6145-6155  
  Keywords Animals; Cell Line, Tumor; Cells, Cultured; Guanidines/chemistry/*pharmacology; Hepatitis B virus/drug effects/genetics/*physiology; Humans; Mice; Organophosphorus Compounds/chemistry/pharmacology; RNA Interference; RNA, Small Interfering/genetics/*pharmacology; Transfection; Virus Replication/*drug effects/genetics; 2â²-O-Guanidinopropyl; Hbv; RNAi; siRNAs  
  Abstract Silencing hepatitis B virus (HBV) gene expression with exogenous activators of the RNA interference (RNAi) pathway has shown promise as a new mode of treating infection with the virus. However, optimizing efficacy, specificity, pharmacokinetics and stability of RNAi activators remains a priority before clinical application of this promising therapeutic approach is realised. Chemical modification of synthetic short interfering RNAs (siRNAs) provides the means to address these goals. This study aimed to assess the benefits of incorporating nucleotides with 2'-O-guanidinopropyl (GP) modifications into siRNAs that target HBV. Single GP residues were incorporated at nucleotide positions from 2 to 21 of the antisense strand of a previously characterised effective antiHBV siRNA. When tested in cultured cells, siRNAs with GP moieties at selected positions improved silencing efficacy. Stability of chemically modified siRNAs in 80% serum was moderately improved and better silencing effects were observed without evidence for toxicity or induction of an interferon response. Moreover, partially complementary target sequences were less susceptible to silencing by siRNAs with GP residues located in the seed region. Hydrodynamic co-injection of siRNAs with a replication-competent HBV plasmid resulted in highly effective knock down of markers of viral replication in mice. Evidence for improved efficacy, reduced off target effects and good silencing in vivo indicate that GP-modifications of siRNAs may be used to enhance their therapeutic utility.  
  Call Number Serial 1014  
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Author (up) Pandey, R.; Chander, R.; Sainis, K.B. file  url
  Title Prodigiosins as anti cancer agents: living upto their name Type Journal Article
  Year 2009 Publication Current Pharmaceutical Design Abbreviated Journal Curr Pharm Des  
  Volume 15 Issue 7 Pages 732-741  
  Keywords Animals; Antineoplastic Agents/chemistry/isolation & purification/*pharmacology/therapeutic use; Apoptosis/drug effects; Cell Cycle/drug effects; Cell Line, Tumor; Cell Survival/drug effects; DNA Damage; Gram-Negative Bacteria/metabolism; Humans; Neoplasms/drug therapy; Prodigiosin/chemistry/isolation & purification/*pharmacology/therapeutic use; Transcription Factors/metabolism  
  Abstract Prodigiosins are a family of bright red colored bacterial pigment and derive their name from the miraculous (prodigious) events associated with their occurrence. They indeed seem to be living upto their name as a host of activities such as anti-microbial, anti-malarial, anti-cancer and immunosuppressive have been associated with them. Out of these, immunosuppressive and anti-cancer activity has received more importance as it has a clinical promise. Prodigiosins, isolated mostly from Gram negative bacteria are characterized by a common pyrryldipyrrylmethene structure with varying side chains. The review discusses the mechanisms involved in the anti-cancer activity of this class of compounds. In vitro, prodigiosins have been shown to primarily target the cancer cells independently of the p53 status while little or no effect has been observed on normal cells. In addition, prodigiosins are effective in cancer cells with multidrug resistance phenotype and defects in the apoptotic pathways. These make prodigiosins attractive candidates for further development. Though the molecular targets of prodigiosins have not been clearly defined, they have been found to target different signaling pathways possibly through induction of DNA double strand breaks and/ or neutralization of pH gradients leading to changes in cell cycle proteins and apoptosis. The review will discuss the recent findings related to the mechanism involved in the anti-cancer activity of this class of molecules.  
  Call Number Serial 1517  
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Author (up) Schoenfeld, J.D.; Sibenaller, Z.A.; Mapuskar, K.A.; Wagner, B.A.; Cramer-Morales, K.L.; Furqan, M.; Sandhu, S.; Carlisle, T.L.; Smith, M.C.; Abu Hejleh, T.; Berg, D.J.; Zhang, J.; Keech, J.; Parekh, K.R.; Bhatia, S.; Monga, V.; Bodeker, K.L.; Ahmann, L.; Vollstedt, S.; Brown, H.; Shanahan Kauffman, E.P.; Schall, M.E.; Hohl, R.J.; Clamon, G.H.; Greenlee, J.D.; Howard, M.A.; Schultz, M.K.; Smith, B.J.; Riley, D.P.; Domann, F.E.; Cullen, J.J.; Buettner, G.R.; Buatti, J.M.; Spitz, D.R.; Allen, B.G. file  url
  Title O2(-) and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate Type Journal Article
  Year 2017 Publication Cancer Cell Abbreviated Journal Cancer Cell  
  Volume 31 Issue 4 Pages 487-500.e8  
  Keywords Animals; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Ascorbic Acid/administration & dosage/adverse effects/*pharmacology; Brain Neoplasms/*drug therapy; Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism/mortality/radiotherapy; Cell Line, Tumor; Chemoradiotherapy/methods; Female; Glioblastoma/*drug therapy/metabolism; Humans; Hydrogen Peroxide/pharmacology; Iron/*metabolism; Lung Neoplasms/*drug therapy/metabolism/mortality/radiotherapy; Male; Mice, Nude; Oxygen/metabolism; Radiation-Sensitizing Agents/pharmacology; Xenograft Model Antitumor Assays; ferritin; glioblastoma multiforme; hydrogen peroxide; labile iron metabolism; non-small cell lung cancer; oxidative stress; pharmacological ascorbate; superoxide; superoxide dismutase; transferrin receptor  
  Abstract Pharmacological ascorbate has been proposed as a potential anti-cancer agent when combined with radiation and chemotherapy. The anti-cancer effects of ascorbate are hypothesized to involve the autoxidation of ascorbate leading to increased steady-state levels of H2O2; however, the mechanism(s) for cancer cell-selective toxicity remain unknown. The current study shows that alterations in cancer cell mitochondrial oxidative metabolism resulting in increased levels of O2(-) and H2O2 are capable of disrupting intracellular iron metabolism, thereby selectively sensitizing non-small-cell lung cancer (NSCLC) and glioblastoma (GBM) cells to ascorbate through pro-oxidant chemistry involving redox-active labile iron and H2O2. In addition, preclinical studies and clinical trials demonstrate the feasibility, selective toxicity, tolerability, and potential efficacy of pharmacological ascorbate in GBM and NSCLC therapy.  
  Call Number Serial 2122  
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Author (up) Tacke, M.; Cuffe, L.P.; Gallagher, W.M.; Lou, Y.; Mendoza, O.; Muller-Bunz, H.; Rehmann, F.-J.K.; Sweeney, N. file  url
doi  openurl
  Title Methoxy-phenyl substituted ansa-titanocenes as potential anti-cancer drugs derived from fulvenes and titanium dichloride Type Journal Article
  Year 2004 Publication Journal of Inorganic Biochemistry Abbreviated Journal J Inorg Biochem  
  Volume 98 Issue 12 Pages 1987-1994  
  Keywords Animals; Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology/toxicity; Carcinoma, Renal Cell/*drug therapy; Cell Line, Tumor; Cyclopentanes/chemical synthesis/chemistry/*pharmacology/toxicity; Drug Evaluation, Preclinical; Inhibitory Concentration 50; Kidney Neoplasms/*drug therapy; Molecular Conformation; Swine; Titanium/*pharmacology/toxicity  
  Abstract Starting from 6-(4'-methoxyphenyl)fulvene (1a), 6-(2',4',6'-trimethoxyphenyl)fulvene (1b), or 6-(3',5'-dimethoxyphenyl)fulvene (1c), [1,2-di(cyclopentadienyl)-1,2-di(4'-methoxyphenyl)-ethanediyl] titanium dichloride (2a), [1,2-di(cyclopentadienyl)-1,2-bis(2',4',6'-trimethoxyphenyl)-ethanediyl] titanium dichloride (2b), and [1,2-di(cyclopentadienyl)-1,2-bis(3',5'-dimethoxyphenyl)-ethanediyl] titanium dichloride (2c) were synthesised. When titanocenes 2a-c were tested against pig kidney carcinoma cells (LLC-PK) inhibitory concentrations (IC50) of 2.8 x 10(-4), 3.6 x 10(-4) and 2.1 x 10(-4) M, respectively, were observed.  
  Call Number Serial 393  
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Author (up) Tang, K.; Zhang, Y.; Zhang, H.; Xu, P.; Liu, J.; Ma, J.; Lv, M.; Li, D.; Katirai, F.; Shen, G.-X.; Zhang, G.; Feng, Z.-H.; Ye, D.; Huang, B. file  url
doi  openurl
  Title Delivery of chemotherapeutic drugs in tumour cell-derived microparticles Type Journal Article
  Year 2012 Publication Nature Communications Abbreviated Journal Nat Commun  
  Volume 3 Issue Pages 1282  
  Keywords Animals; Antineoplastic Agents/*administration & dosage/therapeutic use; Cell Line, Tumor; Cell Membrane/metabolism; Cell-Derived Microparticles/*metabolism; Cisplatin/administration & dosage/therapeutic use; Drug Carriers/*metabolism; Female; Liver Neoplasms/drug therapy; Methotrexate/administration & dosage/therapeutic use; Mice; Mice, Inbred BALB C; Mice, SCID; Neoplasms/*drug therapy; Neoplasms, Experimental; Ovarian Neoplasms/drug therapy  
  Abstract Cellular microparticles are vesicular plasma membrane fragments with a diameter of 100-1,000 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that tumour cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application.  
  Call Number Serial 1080  
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Author (up) Vikram, A.; Jesudhasan, P.R.; Jayaprakasha, G.K.; Pillai, S.D.; Jayaraman, A.; Patil, B.S. file  url
  Title Citrus flavonoid represses Salmonella pathogenicity island 1 and motility in S. Typhimurium LT2 Type Journal Article
  Year 2011 Publication International Journal of Food Microbiology Abbreviated Journal Int J Food Microbiol  
  Volume 145 Issue 1 Pages 28-36  
  Keywords Bacterial Adhesion/drug effects; Bacterial Proteins/drug effects; Biofilms/drug effects/growth & development; Cell Line, Tumor; Citrus/*chemistry; Flagella/drug effects; Flavanones/*pharmacology; Gene Expression Profiling; Gene Expression Regulation, Bacterial; *Genomic Islands; Humans; Oligonucleotide Array Sequence Analysis; Salmonella typhimurium/*drug effects/genetics/growth & development/pathogenicity; Virulence  
  Abstract Salmonellosis is one of the leading health problems worldwide. With the rise of drug resistance strains, it has become imperative to identify alternative strategies to counter bacterial infection. Natural products were used historically to identify novel compounds with various bioactivities. Citrus species is a rich source of flavonoids. Naringenin, a flavonone, is present predominantly in grapefruit. Previously we have demonstrated that naringenin is potent inhibitor of cell-cell signaling. The current study was undertaken to understand the effect of naringenin on Salmonella Typhimurium LT2. The cDNA microarrays were employed to study the response of S. Typhimurium to naringenin treatment. Naringenin specifically repressed 24 genes in the Salmonella pathogenicity island 1 and down-regulated 17 genes involved in flagellar and motility. Furthermore, phenotypic assays support the result of microarray analysis. In addition, naringenin seems to repress SPI-1 in pstS/hilD-dependent manner. Altogether the data suggest that naringenin attenuated S. Typhimurium virulence and cell motility. This is the first molecular evidence to demonstrate effect of naringenin on bacterial virulence and cell motility.  
  Call Number Serial 1580  
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