Cardiac Glycoside Glucoevatromonoside Induces Cancer Type-Specific Cell Death
Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanom...
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Published in: | Frontiers in pharmacology Vol. 9; p. 70 |
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Abstract | Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC) and high-affinity binding to the Na
/K
-ATPase α subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission electron microscopy, live cell imaging and flow cytometry. This non-canonical cell death was not preceded or accompanied by exacerbation of autophagy. In the presence of GEV, markers of autophagic flux (e.g. LC3I-II conversion) were impacted, even in presence of bafilomycin A1. Cell death induction remained unaffected by calpain, cathepsin, parthanatos, or necroptosis inhibitors. Interestingly, GEV triggered caspase-dependent apoptosis in U937 acute myeloid leukemia cells, witnessing cancer-type specific cell death induction. Differential cell cycle modulation by this CG led to a G2/M arrest, cyclin B1 and p53 downregulation in A549, but not in U937 cells. We further extended the anti-cancer potential of GEV to 3D cell culture using clonogenic and spheroid formation assays and validated our findings
by zebrafish xenografts. Altogether, GEV shows an interesting anticancer profile with the ability to exert cytotoxic effects via induction of different cell death modalities. |
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AbstractList | Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC) and high-affinity binding to the Na+/K+-ATPase α subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission electron microscopy, live cell imaging and flow cytometry. This non-canonical cell death was not preceded or accompanied by exacerbation of autophagy. In the presence of GEV, markers of autophagic flux (e.g. LC3I-II conversion) were impacted, even in presence of bafilomycin A1. Cell death induction remained unaffected by calpain, cathepsin, parthanatos, or necroptosis inhibitors. Interestingly, GEV triggered caspase-dependent apoptosis in U937 acute myeloid leukemia cells, witnessing cancer-type specific cell death induction. Differential cell cycle modulation by this CG led to a G2/M arrest, cyclin B1 and p53 downregulation in A549, but not in U937 cells. We further extended the anti-cancer potential of GEV to 3D cell culture using clonogenic and spheroid formation assays and validated our findings in vivo by zebrafish xenografts. Altogether, GEV shows an interesting anticancer profile with the ability to exert cytotoxic effects via induction of different cell death modalities. Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC) and high-affinity binding to the Na + /K + -ATPase α subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission electron microscopy, live cell imaging and flow cytometry. This non-canonical cell death was not preceded or accompanied by exacerbation of autophagy. In the presence of GEV, markers of autophagic flux (e.g. LC3I-II conversion) were impacted, even in presence of bafilomycin A1. Cell death induction remained unaffected by calpain, cathepsin, parthanatos, or necroptosis inhibitors. Interestingly, GEV triggered caspase-dependent apoptosis in U937 acute myeloid leukemia cells, witnessing cancer-type specific cell death induction. Differential cell cycle modulation by this CG led to a G2/M arrest, cyclin B1 and p53 downregulation in A549, but not in U937 cells. We further extended the anti-cancer potential of GEV to 3D cell culture using clonogenic and spheroid formation assays and validated our findings in vivo by zebrafish xenografts. Altogether, GEV shows an interesting anticancer profile with the ability to exert cytotoxic effects via induction of different cell death modalities. Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC) and high-affinity binding to the Na /K -ATPase α subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission electron microscopy, live cell imaging and flow cytometry. This non-canonical cell death was not preceded or accompanied by exacerbation of autophagy. In the presence of GEV, markers of autophagic flux (e.g. LC3I-II conversion) were impacted, even in presence of bafilomycin A1. Cell death induction remained unaffected by calpain, cathepsin, parthanatos, or necroptosis inhibitors. Interestingly, GEV triggered caspase-dependent apoptosis in U937 acute myeloid leukemia cells, witnessing cancer-type specific cell death induction. Differential cell cycle modulation by this CG led to a G2/M arrest, cyclin B1 and p53 downregulation in A549, but not in U937 cells. We further extended the anti-cancer potential of GEV to 3D cell culture using clonogenic and spheroid formation assays and validated our findings by zebrafish xenografts. Altogether, GEV shows an interesting anticancer profile with the ability to exert cytotoxic effects via induction of different cell death modalities. |
Author | Munkert, Jennifer Schneider, Naira F Z Christov, Christo Cerella, Claudia Lee, Jin-Young Mazumder, Aloran Simões, Cláudia M O de Carvalho, Annelise Han, Byung Woo Kim, Hyun-Jung Kim, Kyung Rok Kreis, Wolfgang Kim, Kyu-Won Braga, Fernão C Diederich, Marc Pádua, Rodrigo M Dicato, Mario |
AuthorAffiliation | 6 SNU-Harvard Neurovascular Protection Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , Seoul , South Korea 4 Department of Biology, Friedrich-Alexander Universität, Erlangen-Nürnberg , Erlangen , Germany 5 Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil 1 Laboratorio de Virologia Applicada, Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina , Florianópolis , Brazil 2 Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg , Luxembourg , Luxembourg 8 College of Pharmacy, Chung-Ang University , Seoul , South Korea 7 Faculté de Médecine, Université de Lorraine , Nancy , France 3 Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul , South Korea |
AuthorAffiliation_xml | – name: 4 Department of Biology, Friedrich-Alexander Universität, Erlangen-Nürnberg , Erlangen , Germany – name: 6 SNU-Harvard Neurovascular Protection Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , Seoul , South Korea – name: 5 Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais , Belo Horizonte , Brazil – name: 1 Laboratorio de Virologia Applicada, Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina , Florianópolis , Brazil – name: 2 Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg , Luxembourg , Luxembourg – name: 3 Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul , South Korea – name: 8 College of Pharmacy, Chung-Ang University , Seoul , South Korea – name: 7 Faculté de Médecine, Université de Lorraine , Nancy , France |
Author_xml | – sequence: 1 givenname: Naira F Z surname: Schneider fullname: Schneider, Naira F Z organization: Laboratorio de Virologia Applicada, Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis, Brazil – sequence: 2 givenname: Claudia surname: Cerella fullname: Cerella, Claudia organization: Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea – sequence: 3 givenname: Jin-Young surname: Lee fullname: Lee, Jin-Young organization: Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea – sequence: 4 givenname: Aloran surname: Mazumder fullname: Mazumder, Aloran organization: Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea – sequence: 5 givenname: Kyung Rok surname: Kim fullname: Kim, Kyung Rok organization: Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea – sequence: 6 givenname: Annelise surname: de Carvalho fullname: de Carvalho, Annelise organization: Laboratorio de Virologia Applicada, Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis, Brazil – sequence: 7 givenname: Jennifer surname: Munkert fullname: Munkert, Jennifer organization: Department of Biology, Friedrich-Alexander Universität, Erlangen-Nürnberg, Erlangen, Germany – sequence: 8 givenname: Rodrigo M surname: Pádua fullname: Pádua, Rodrigo M organization: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil – sequence: 9 givenname: Wolfgang surname: Kreis fullname: Kreis, Wolfgang organization: Department of Biology, Friedrich-Alexander Universität, Erlangen-Nürnberg, Erlangen, Germany – sequence: 10 givenname: Kyu-Won surname: Kim fullname: Kim, Kyu-Won organization: SNU-Harvard Neurovascular Protection Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea – sequence: 11 givenname: Christo surname: Christov fullname: Christov, Christo organization: Faculté de Médecine, Université de Lorraine, Nancy, France – sequence: 12 givenname: Mario surname: Dicato fullname: Dicato, Mario organization: Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, Luxembourg, Luxembourg – sequence: 13 givenname: Hyun-Jung surname: Kim fullname: Kim, Hyun-Jung organization: College of Pharmacy, Chung-Ang University, Seoul, South Korea – sequence: 14 givenname: Byung Woo surname: Han fullname: Han, Byung Woo organization: Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea – sequence: 15 givenname: Fernão C surname: Braga fullname: Braga, Fernão C organization: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil – sequence: 16 givenname: Cláudia M O surname: Simões fullname: Simões, Cláudia M O organization: Laboratorio de Virologia Applicada, Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis, Brazil – sequence: 17 givenname: Marc surname: Diederich fullname: Diederich, Marc organization: Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea |
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Cites_doi | 10.1038/onc.2015.455 10.1016/j.bcp.2010.10.013 10.1038/msb.2011.75 10.1016/j.steroids.2014.12.015 10.1007/s00432-002-0359-9 10.1016/j.biocel.2010.11.009 10.1016/j.colsurfb.2016.01.027 10.1021/acs.jnatprod.5b01055 10.1186/1741-7007-9-38 10.1016/j.jsbmb.2015.03.008 10.1158/1535-7163.MCT-11-0421 10.1124/mi.8.1.8 10.1126/scitranslmed.3003807 10.1007/s10637-006-7772-x 10.2174/092986712798992075 10.1016/j.biopha.2017.10.128 10.1016/j.antiviral.2011.06.015 10.1016/j.cbi.2009.10.012 10.1016/j.bbamem.2007.04.012 10.1016/j.biocel.2012.06.028 10.18632/oncotarget.6832 10.1021/np5000796 10.1016/j.taap.2011.10.007 10.1007/s10637-013-9984-1 10.1177/1534735407309623 10.1016/j.bcp.2010.08.025 10.1073/pnas.1222308110 10.1158/0008-5472.CAN-09-0891 10.1107/S0907444910007493 10.1111/j.1582-4934.2009.00708.x 10.1111/j.1749-6632.2009.04723.x 10.1016/j.jconrel.2009.01.020 10.1007/s12263-011-0231-0 10.4161/onci.23082 10.1038/cddis.2015.134 10.1016/j.ctrv.2007.11.003 10.1016/B978-0-12-407695-2.00007-X 10.18632/oncotarget.7497 10.1016/j.jsbmb.2010.12.016 10.1016/j.mito.2012.06.003 10.1593/neo.07928 10.1097/00001813-200108000-00012 10.1007/s10637-014-0127-0 10.1038/nrd2907 10.1111/j.1600-0714.1999.tb02000.x 10.1016/j.semcancer.2016.06.001 10.1309/54H4Q88A1UBBWPTE 10.1002/jcc.21334 10.3747/co.19.1113 10.1016/j.bcp.2016.08.017 10.1016/j.fct.2013.10.020 10.1158/1535-7163.MCT-07-2241 10.1073/pnas.1422997112 10.1054/mehy.1999.0985 10.1158/1535-7163.MCT-05-0367 10.1016/j.bcp.2013.10.027 10.1073/pnas.92.12.5386 10.1016/S0021-9673(96)00645-0 |
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Copyright | Copyright © 2018 Schneider, Cerella, Lee, Mazumder, Kim, de Carvalho, Munkert, Pádua, Kreis, Kim, Christov, Dicato, Kim, Han, Braga, Simões and Diederich. 2018 Schneider, Cerella, Lee, Mazumder, Kim, de Carvalho, Munkert, Pádua, Kreis, Kim, Christov, Dicato, Kim, Han, Braga, Simões and Diederich |
Copyright_xml | – notice: Copyright © 2018 Schneider, Cerella, Lee, Mazumder, Kim, de Carvalho, Munkert, Pádua, Kreis, Kim, Christov, Dicato, Kim, Han, Braga, Simões and Diederich. 2018 Schneider, Cerella, Lee, Mazumder, Kim, de Carvalho, Munkert, Pádua, Kreis, Kim, Christov, Dicato, Kim, Han, Braga, Simões and Diederich |
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Keywords | lung cancer non-canonical cell death apoptosis cardiac glycoside glucoevatromonoside |
Language | English |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology Edited by: Thomas Efferth, Johannes Gutenberg-Universität Mainz, Germany Reviewed by: Linlin Lu, International Institute for Translational Chinese Medicine, China; Wentzel Christoffel Gelderblom, Cape Peninsula University of Technology, South Africa These authors have contributed equally to this work. |
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References | Stenkvist (B52) 2001; 12 Newman (B42) 2008; 8 Laursen (B29) 2013; 110 Slingerland (B50) 2013; 31 Mijatovic (B38) 2006; 5 Castro Braga (B2) 1996; 756 Menger (B34) 2012; 4 Radogna (B45) 2016; 35 Mijatovic (B36) 2008; 7 Zeino (B61) 2015; 150 Cerella (B6) 2015; 6 Kang (B24) 2016; 7 Mijatovic (B37) 2012; 19 Schneider (B46) 2018; 97 Nakayama (B39) 2013; 305 Diederich (B9) 2016 Hong (B19) 2014; 32 Laursen (B28) 2015; 112 Sievers (B49) 2011; 7 Mashal (B31) 1996; 56 Newman (B40) 2016; 79 Dutta (B12) 1995; 92 Kulikov (B25) 2007; 1768 Tsvetkova (B55) 2012; 19 Schumacher (B48) 2011; 6 Wang (B56) 2012; 44 Menger (B35) 2013; 2 Wang (B57) 2009; 69 Feng (B16) 2010; 183 Hsu (B20) 2016; 7 Xu (B58) 2011; 125 Duenas-Gonzalez (B11) 2008; 34 Mathieu (B32) 2009; 13 Juncker (B23) 2011; 81 Trott (B54) 2010; 31 Farah (B15) 2016; 141 Newman (B41) 2007; 6 Diederich (B10) 2017; 125 Bertol (B1) 2011; 92 Soria (B51) 2000; 60 Cerella (B5) 2013; 13 Prassas (B44) 2011; 10 Yasuda (B60) 2002; 128 Hundeshagen (B22) 2011; 9 Pongrakhananon (B43) 2014; 88 Lapenna (B27) 2009; 8 Lefranc (B30) 2008; 10 Mekhail (B33) 2006; 24 Elbaz (B13) 2012; 258 Grabsch (B17) 2004; 122 Schnekenburger (B47) 2011; 81 Czepukojc (B8) 2014; 64 Cerella (B3) 2011; 43 Kushner (B26) 1999; 28 Cerella (B4) 2009; 1171 Haux (B18) 1999; 53 Xue (B59) 2015; 94 Emsley (B14) 2010; 66 Hu (B21) 2009; 135 Svensson (B53) 2005; 25 Cragg (B7) 2014; 77 |
References_xml | – volume: 35 start-page: 3839 year: 2016 ident: B45 article-title: Cell type-dependent ROS and mitophagy response leads to apoptosis or necroptosis in neuroblastoma publication-title: Oncogene doi: 10.1038/onc.2015.455 contributor: fullname: Radogna – volume: 81 start-page: 364 year: 2011 ident: B47 article-title: Sustained exposure to the DNA demethylating agent, 2'-deoxy-5-azacytidine, leads to apoptotic cell death in chronic myeloid leukemia by promoting differentiation, senescence, and autophagy publication-title: Biochem. Pharmacol. doi: 10.1016/j.bcp.2010.10.013 contributor: fullname: Schnekenburger – volume: 56 start-page: 4159 year: 1996 ident: B31 article-title: Expression of cell cycle-regulated proteins in prostate cancer publication-title: Cancer Res. contributor: fullname: Mashal – volume: 7 start-page: 539 year: 2011 ident: B49 article-title: Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal omega publication-title: Mol. Syst. Biol. doi: 10.1038/msb.2011.75 contributor: fullname: Sievers – volume: 25 start-page: 207 year: 2005 ident: B53 article-title: Digoxin inhibits neuroblastoma tumor growth in mice publication-title: Anticancer Res. contributor: fullname: Svensson – volume: 94 start-page: 51 year: 2015 ident: B59 article-title: TXA9, a cardiac glycoside from Streptocaulon juventas, exerts a potent anti-tumor activity against human non-small cell lung cancer cells in vitro and in vivo publication-title: Steroids doi: 10.1016/j.steroids.2014.12.015 contributor: fullname: Xue – volume: 128 start-page: 412 year: 2002 ident: B60 article-title: Overexpression of cyclin B1 in gastric cancer and its clinicopathological significance: an immunohistological study publication-title: J. Cancer Res. Clin. Oncol. doi: 10.1007/s00432-002-0359-9 contributor: fullname: Yasuda – volume: 43 start-page: 393 year: 2011 ident: B3 article-title: Magnetic fields promote a pro-survival non-capacitative Ca2+ entry via phospholipase C signaling publication-title: Int. J. Biochem. Cell Biol. doi: 10.1016/j.biocel.2010.11.009 contributor: fullname: Cerella – volume: 141 start-page: 158 year: 2016 ident: B15 article-title: Silver nanoparticles synthesized from Adenium obesum leaf extract induced DNA damage, apoptosis and autophagy via generation of reactive oxygen species publication-title: Colloids Surf. B Biointerfaces doi: 10.1016/j.colsurfb.2016.01.027 contributor: fullname: Farah – volume: 79 start-page: 629 year: 2016 ident: B40 article-title: Natural products as sources of new drugs from 1981 to 2014 publication-title: J. Nat. Prod. doi: 10.1021/acs.jnatprod.5b01055 contributor: fullname: Newman – volume: 9 start-page: 38 year: 2011 ident: B22 article-title: Concurrent detection of autolysosome formation and lysosomal degradation by flow cytometry in a high-content screen for inducers of autophagy publication-title: BMC Biol. doi: 10.1186/1741-7007-9-38 contributor: fullname: Hundeshagen – volume: 150 start-page: 97 year: 2015 ident: B61 article-title: Cytotoxicity of cardiotonic steroids in sensitive and multidrug-resistant leukemia cells and the link with Na(+)/K(+)-ATPase publication-title: J. Steroid Biochem. Mol. Biol. doi: 10.1016/j.jsbmb.2015.03.008 contributor: fullname: Zeino – volume: 10 start-page: 2083 year: 2011 ident: B44 article-title: Digitoxin-induced cytotoxicity in cancer cells is mediated through distinct kinase and interferon signaling networks publication-title: Mol. Cancer Ther. doi: 10.1158/1535-7163.MCT-11-0421 contributor: fullname: Prassas – volume: 8 start-page: 36 year: 2008 ident: B42 article-title: Cardiac glycosides as novel cancer therapeutic agents publication-title: Mol. Interv. doi: 10.1124/mi.8.1.8 contributor: fullname: Newman – volume: 4 start-page: 143ra99 year: 2012 ident: B34 article-title: Cardiac glycosides exert anticancer effects by inducing immunogenic cell death publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.3003807 contributor: fullname: Menger – volume: 24 start-page: 423 year: 2006 ident: B33 article-title: Phase 1 trial of Anvirzel in patients with refractory solid tumors publication-title: Invest. New Drugs doi: 10.1007/s10637-006-7772-x contributor: fullname: Mekhail – volume: 19 start-page: 627 year: 2012 ident: B37 article-title: Cardiotonic steroids-mediated targeting of the Na(+)/K(+)-ATPase to combat chemoresistant cancers publication-title: Curr. Med. Chem. doi: 10.2174/092986712798992075 contributor: fullname: Mijatovic – volume: 97 start-page: 684 year: 2018 ident: B46 article-title: Cytotoxic and cytostatic effects of digitoxigenin monodigitoxoside (DGX) in human lung cancer cells and its link to Na,K-ATPase publication-title: Biomed. Pharmacother. doi: 10.1016/j.biopha.2017.10.128 contributor: fullname: Schneider – volume: 92 start-page: 73 year: 2011 ident: B1 article-title: Antiherpes activity of glucoevatromonoside, a cardenolide isolated from a Brazilian cultivar of Digitalis lanata publication-title: Antiviral Res. doi: 10.1016/j.antiviral.2011.06.015 contributor: fullname: Bertol – volume: 183 start-page: 142 year: 2010 ident: B16 article-title: 2'-epi-2'-O-Acetylthevetin B extracted from seeds of Cerbera manghas L. induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells publication-title: Chem. Biol. Interact. doi: 10.1016/j.cbi.2009.10.012 contributor: fullname: Feng – volume: 1768 start-page: 1691 year: 2007 ident: B25 article-title: Ouabain activates signaling pathways associated with cell death in human neuroblastoma publication-title: Biochim. Biophys. Acta doi: 10.1016/j.bbamem.2007.04.012 contributor: fullname: Kulikov – volume: 44 start-page: 1813 year: 2012 ident: B56 article-title: Cardiac glycosides induce autophagy in human non-small cell lung cancer cells through regulation of dual signaling pathways publication-title: Int. J. Biochem. Cell Biol. doi: 10.1016/j.biocel.2012.06.028 contributor: fullname: Wang – volume: 7 start-page: 6074 year: 2016 ident: B24 article-title: Lanatoside C suppressed colorectal cancer cell growth by inducing mitochondrial dysfunction and increased radiation sensitivity by impairing DNA damage repair publication-title: Oncotarget doi: 10.18632/oncotarget.6832 contributor: fullname: Kang – volume: 77 start-page: 703 year: 2014 ident: B7 article-title: New horizons for old drugs and drug leads publication-title: J. Nat. Prod. doi: 10.1021/np5000796 contributor: fullname: Cragg – volume: 258 start-page: 51 year: 2012 ident: B13 article-title: Digitoxin and a synthetic monosaccharide analog inhibit cell viability in lung cancer cells publication-title: Toxicol. Appl. Pharmacol. doi: 10.1016/j.taap.2011.10.007 contributor: fullname: Elbaz – volume: 31 start-page: 1087 year: 2013 ident: B50 article-title: Cardiac glycosides in cancer therapy: from preclinical investigations towards clinical trials publication-title: Invest. New Drugs doi: 10.1007/s10637-013-9984-1 contributor: fullname: Slingerland – volume: 60 start-page: 4000 year: 2000 ident: B51 article-title: Overexpression of cyclin B1 in early-stage non-small cell lung cancer and its clinical implication publication-title: Cancer Res. contributor: fullname: Soria – volume: 6 start-page: 354 year: 2007 ident: B41 article-title: Autophagic cell death of human pancreatic tumor cells mediated by oleandrin, a lipid-soluble cardiac glycoside publication-title: Integr. Cancer Ther. doi: 10.1177/1534735407309623 contributor: fullname: Newman – volume: 81 start-page: 13 year: 2011 ident: B23 article-title: UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells publication-title: Biochem. Pharmacol. doi: 10.1016/j.bcp.2010.08.025 contributor: fullname: Juncker – volume: 110 start-page: 10958 year: 2013 ident: B29 article-title: Crystal structure of the high-affinity Na+K+-ATPase-ouabain complex with Mg2+ bound in the cation binding site publication-title: Proc. Natl. Acad. Sci. U.S.A. doi: 10.1073/pnas.1222308110 contributor: fullname: Laursen – volume: 69 start-page: 6556 year: 2009 ident: B57 article-title: Cardiac glycosides inhibit p53 synthesis by a mechanism relieved by Src or MAPK inhibition publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-09-0891 contributor: fullname: Wang – volume: 66 start-page: 486 year: 2010 ident: B14 article-title: Features and development of Coot publication-title: Acta Crystallogr. D Biol. Crystallogr. doi: 10.1107/S0907444910007493 contributor: fullname: Emsley – volume: 13 start-page: 3960 year: 2009 ident: B32 article-title: The sodium pump α1 sub-unit: a disease progression-related target for metastatic melanoma treatment publication-title: J. Cell. Mol. Med. doi: 10.1111/j.1582-4934.2009.00708.x contributor: fullname: Mathieu – volume: 1171 start-page: 583 year: 2009 ident: B4 article-title: Subapoptogenic oxidative stress strongly increases the activity of the glycolytic key enzyme glyceraldehyde 3-phosphate dehydrogenase publication-title: Ann. N.Y. Acad. Sci. doi: 10.1111/j.1749-6632.2009.04723.x contributor: fullname: Cerella – volume: 135 start-page: 250 year: 2009 ident: B21 article-title: Digoxigenin modification of adenovirus to spatially control gene delivery from chitosan surfaces publication-title: J. Control. Release doi: 10.1016/j.jconrel.2009.01.020 contributor: fullname: Hu – volume: 6 start-page: 89 year: 2011 ident: B48 article-title: Natural compounds as inflammation inhibitors publication-title: Genes Nutr. doi: 10.1007/s12263-011-0231-0 contributor: fullname: Schumacher – volume: 2 start-page: e23082 year: 2013 ident: B35 article-title: Trial watch: cardiac glycosides and cancer therapy publication-title: Oncoimmunology doi: 10.4161/onci.23082 contributor: fullname: Menger – volume: 6 start-page: e1782 year: 2015 ident: B6 article-title: Early downregulation of Mcl-1 regulates apoptosis triggered by cardiac glycoside UNBS1450 publication-title: Cell Death Dis. doi: 10.1038/cddis.2015.134 contributor: fullname: Cerella – volume: 34 start-page: 206 year: 2008 ident: B11 article-title: Valproic acid as epigenetic cancer drug: preclinical, clinical and transcriptional effects on solid tumors publication-title: Cancer Treat. Rev. doi: 10.1016/j.ctrv.2007.11.003 contributor: fullname: Duenas-Gonzalez – volume: 305 start-page: 303 year: 2013 ident: B39 article-title: Role of cyclin B1 levels in DNA damage and DNA damage-induced senescence publication-title: Int. Rev. Cell Mol. Biol. doi: 10.1016/B978-0-12-407695-2.00007-X contributor: fullname: Nakayama – volume: 7 start-page: 62925 year: 2016 ident: B20 article-title: Targeting FXYD2 by cardiac glycosides potently blocks tumor growth in ovarian clear cell carcinoma publication-title: Oncotarget doi: 10.18632/oncotarget.7497 contributor: fullname: Hsu – volume: 125 start-page: 181 year: 2011 ident: B58 article-title: Cardiotonic steroids attenuate ERK phosphorylation and generate cell cycle arrest to block human hepatoma cell growth publication-title: J. Steroid Biochem. Mol. Biol. doi: 10.1016/j.jsbmb.2010.12.016 contributor: fullname: Xu – volume: 13 start-page: 225 year: 2013 ident: B5 article-title: Assembling the puzzle of anti-cancer mechanisms triggered by cardiac glycosides publication-title: Mitochondrion doi: 10.1016/j.mito.2012.06.003 contributor: fullname: Cerella – volume: 10 start-page: 198 year: 2008 ident: B30 article-title: The sodium pump α1 subunit as a potential target to combat apoptosis-resistant glioblastomas publication-title: Neoplasia doi: 10.1593/neo.07928 contributor: fullname: Lefranc – volume: 12 start-page: 635 year: 2001 ident: B52 article-title: Cardenolides and cancer publication-title: Anticancer. Drugs doi: 10.1097/00001813-200108000-00012 contributor: fullname: Stenkvist – volume: 32 start-page: 1204 year: 2014 ident: B19 article-title: First-in-human study of pbi-05204, an oleander-derived inhibitor of akt, fgf-2, nf-kappaBeta and p70s6k, in patients with advanced solid tumors publication-title: Invest. New Drugs doi: 10.1007/s10637-014-0127-0 contributor: fullname: Hong – volume: 8 start-page: 547 year: 2009 ident: B27 article-title: Cell cycle kinases as therapeutic targets for cancer publication-title: Nat. Rev. Drug Discov. doi: 10.1038/nrd2907 contributor: fullname: Lapenna – volume: 28 start-page: 77 year: 1999 ident: B26 article-title: Aberrant expression of cyclin A and cyclin B1 proteins in oral carcinoma publication-title: J. Oral Pathol. Med. doi: 10.1111/j.1600-0714.1999.tb02000.x contributor: fullname: Kushner – start-page: 4 year: 2016 ident: B9 article-title: Non-canonical programmed cell death mechanisms triggered by natural compounds publication-title: Semin. Cancer Biol. doi: 10.1016/j.semcancer.2016.06.001 contributor: fullname: Diederich – volume: 122 start-page: 511 year: 2004 ident: B17 article-title: Prognostic value of cyclin B1 protein expression in colorectal cancer publication-title: Am. J. Clin. Pathol. doi: 10.1309/54H4Q88A1UBBWPTE contributor: fullname: Grabsch – volume: 31 start-page: 455 year: 2010 ident: B54 article-title: AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading publication-title: J. Comput. Chem. doi: 10.1002/jcc.21334 contributor: fullname: Trott – volume: 19 start-page: S45 year: 2012 ident: B55 article-title: Drug resistance and its significance for treatment decisions in non-small-cell lung cancer publication-title: Curr. Oncol. doi: 10.3747/co.19.1113 contributor: fullname: Tsvetkova – volume: 125 start-page: 1 year: 2017 ident: B10 article-title: Cardiac glycosides: from molecular targets to immunogenic cell death publication-title: Biochem. Pharmacol. doi: 10.1016/j.bcp.2016.08.017 contributor: fullname: Diederich – volume: 64 start-page: 249 year: 2014 ident: B8 article-title: Synthetic polysulfane derivatives induce cell cycle arrest and apoptotic cell death in human hematopoietic cancer cells publication-title: Food Chem. Toxicol. doi: 10.1016/j.fct.2013.10.020 contributor: fullname: Czepukojc – volume: 7 start-page: 1285 year: 2008 ident: B36 article-title: Nucleolus and c-Myc: potential targets of cardenolide-mediated antitumor activity publication-title: Mol. Cancer Ther. doi: 10.1158/1535-7163.MCT-07-2241 contributor: fullname: Mijatovic – volume: 112 start-page: 1755 year: 2015 ident: B28 article-title: Structures and characterization of digoxin- and bufalin-bound Na+,K+-ATPase compared with the ouabain-bound complex publication-title: Proc. Natl. Acad. Sci. U.S.A. doi: 10.1073/pnas.1422997112 contributor: fullname: Laursen – volume: 53 start-page: 543 year: 1999 ident: B18 article-title: Digitoxin is a potential anticancer agent for several types of cancer publication-title: Med. Hypotheses doi: 10.1054/mehy.1999.0985 contributor: fullname: Haux – volume: 5 start-page: 391 year: 2006 ident: B38 article-title: The cardenolide UNBS1450 is able to deactivate nuclear factor kappaB-mediated cytoprotective effects in human non-small cell lung cancer cells publication-title: Mol. Cancer Ther. doi: 10.1158/1535-7163.MCT-05-0367 contributor: fullname: Mijatovic – volume: 88 start-page: 23 year: 2014 ident: B43 article-title: Monosaccharide digitoxin derivative sensitize human non-small cell lung cancer cells to anoikis through Mcl-1 proteasomal degradation publication-title: Biochem. Pharmacol. doi: 10.1016/j.bcp.2013.10.027 contributor: fullname: Pongrakhananon – volume: 92 start-page: 5386 year: 1995 ident: B12 article-title: Cyclins as markers of tumor proliferation: immunocytochemical studies in breast cancer publication-title: Proc. Natl. Acad. Sci. U.S.A. doi: 10.1073/pnas.92.12.5386 contributor: fullname: Dutta – volume: 756 start-page: 287 year: 1996 ident: B2 article-title: Isolation of cardenolides from a Brazilian cultivar of Digitalis lanata by rotation locular counter-current chromatography publication-title: J. Chromatogr. A doi: 10.1016/S0021-9673(96)00645-0 contributor: fullname: Castro Braga |
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Title | Cardiac Glycoside Glucoevatromonoside Induces Cancer Type-Specific Cell Death |
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