Zebularine-induced myeloma cell death is accompanied by decreased c-Myc expression

go back to reference S.B. Baylin, M. Esteller, M.R. Rountree, K.E. Bachman, K. Schuebel, J.G. Herman, Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum. Mol. Genet. 10, 687–692 (2001)CrossRef S.B. Baylin, M. Esteller, M.R. Rountree, K.E. Bachman, K. Schuebel, J.G. Herman, Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum. Mol. Genet. 10, 687–692 (2001)CrossRef

go back to reference B.A. Walker, C.P. Wardell, L. Chiecchio, E.M. Smith, K.D. Boyd, A. Neri, F.E. Davies, F.M. Ross, G.J. Morgan, Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma. Blood 117, 553–562 (2011)CrossRef B.A. Walker, C.P. Wardell, L. Chiecchio, E.M. Smith, K.D. Boyd, A. Neri, F.E. Davies, F.M. Ross, G.J. Morgan, Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma. Blood 117, 553–562 (2011)CrossRef

go back to reference E. Braggio, A. Maiolino, M.E. Gouveia, R. Magalhães, J.T. Souto Filho, M. Garnica, M. Nucci, I.Z. Renault, Methylation status of nine tumor suppressor genes in multiple myeloma. Int. J. Hematol. 91, 87–96 (2010)CrossRef E. Braggio, A. Maiolino, M.E. Gouveia, R. Magalhães, J.T. Souto Filho, M. Garnica, M. Nucci, I.Z. Renault, Methylation status of nine tumor suppressor genes in multiple myeloma. Int. J. Hematol. 91, 87–96 (2010)CrossRef

go back to reference C.M. Bender, M.L. Gonzalgo, F.A. Gonzales, C.T. Nguyen, K.D. Robertson, P.A. Jones, Roles of cell division and gene transcription in the methylation of CpG Islands. Mol. Cell. Biol. 19, 6690–6698 (1999)CrossRef C.M. Bender, M.L. Gonzalgo, F.A. Gonzales, C.T. Nguyen, K.D. Robertson, P.A. Jones, Roles of cell division and gene transcription in the methylation of CpG Islands. Mol. Cell. Biol. 19, 6690–6698 (1999)CrossRef

go back to reference K. Maes, E. De Smedt, M. Lemaire, H. De Raeve, E. Menu, E. Van Valckenborgh, S. McClue, K. Vanderkerken, E. De Bruyne, The role of DNA damage and repair in decitabine-mediated apoptosis in multiple myeloma. Oncotarget 5, 3115–3129 (2014)CrossRef K. Maes, E. De Smedt, M. Lemaire, H. De Raeve, E. Menu, E. Van Valckenborgh, S. McClue, K. Vanderkerken, E. De Bruyne, The role of DNA damage and repair in decitabine-mediated apoptosis in multiple myeloma. Oncotarget 5, 3115–3129 (2014)CrossRef

go back to reference T. Kiziltepe, T. Hideshima, L. Catley, N. Raje, H. Yasui, N. Shiraishi, Y. Okawa, H. Ikeda, S. Vallet, S. Pozzi, K. Ishitsuka, E.M. Ocio, D. Chauhan, K.C. Anderson, 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells. Mol. Cancer Ther. 6, 1718–1727 (2007)CrossRef T. Kiziltepe, T. Hideshima, L. Catley, N. Raje, H. Yasui, N. Shiraishi, Y. Okawa, H. Ikeda, S. Vallet, S. Pozzi, K. Ishitsuka, E.M. Ocio, D. Chauhan, K.C. Anderson, 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells. Mol. Cancer Ther. 6, 1718–1727 (2007)CrossRef

go back to reference J. Laliberté, V.E. Marquez, R.L. Momparler, Potent inhibitors for the deamination of cytosine arabinoside and 5-aza-2′-deoxycytidine by human cytidine deaminase. Cancer Chemother. Pharmacol. 30, 7–11 (1992)CrossRef J. Laliberté, V.E. Marquez, R.L. Momparler, Potent inhibitors for the deamination of cytosine arabinoside and 5-aza-2′-deoxycytidine by human cytidine deaminase. Cancer Chemother. Pharmacol. 30, 7–11 (1992)CrossRef

go back to reference B.A. Chabner, J.C. Drake, D.G. Johns, Deamination of 5-azacytidine by a human leukemia cell cytidine deaminase. Biochem. Pharmacol. 22, 2763–2765 (1973)CrossRef B.A. Chabner, J.C. Drake, D.G. Johns, Deamination of 5-azacytidine by a human leukemia cell cytidine deaminase. Biochem. Pharmacol. 22, 2763–2765 (1973)CrossRef

go back to reference C. Stresemann, B. Brueckner, T. Musch, H. Stopper, F. Lyko, Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines. Cancer Res. 66, 2794–2800 (2006)CrossRef C. Stresemann, B. Brueckner, T. Musch, H. Stopper, F. Lyko, Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines. Cancer Res. 66, 2794–2800 (2006)CrossRef

go back to reference L. Zhou, X. Cheng, B.A. Connolly, M.J. Dickman, P.J. Hurd, D.P. Hornby, Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J. Mol. Biol. 321, 591–599 (2002)CrossRef L. Zhou, X. Cheng, B.A. Connolly, M.J. Dickman, P.J. Hurd, D.P. Hornby, Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J. Mol. Biol. 321, 591–599 (2002)CrossRef

go back to reference J.C. Cheng, C.B. Yoo, D.J. Weisenberger, J. Chuang, C. Wozniak, G. Liang, V.E. Marquez, S. Greer, T.F. Orntoft, T. Thykjaer, P.A. Jones, Preferential response of cancer cells to zebularine. Cancer Cell 6, 151–158 (2004)CrossRef J.C. Cheng, C.B. Yoo, D.J. Weisenberger, J. Chuang, C. Wozniak, G. Liang, V.E. Marquez, S. Greer, T.F. Orntoft, T. Thykjaer, P.A. Jones, Preferential response of cancer cells to zebularine. Cancer Cell 6, 151–158 (2004)CrossRef

go back to reference P. Krzeminski, M.E. Sarasquete, I. Misiewicz-Krzeminska, R. Corral, L.A. Corchete, A.A. Martín, R. García-Sanz, J.F. San Miguel, N.C. Gutiérrez, Insights into epigenetic regulation of microRNA-155 expression in multiple myeloma. Biochim. Biophys. Acta 1849, 353–366 (2015)CrossRef P. Krzeminski, M.E. Sarasquete, I. Misiewicz-Krzeminska, R. Corral, L.A. Corchete, A.A. Martín, R. García-Sanz, J.F. San Miguel, N.C. Gutiérrez, Insights into epigenetic regulation of microRNA-155 expression in multiple myeloma. Biochim. Biophys. Acta 1849, 353–366 (2015)CrossRef

go back to reference J. Sambrook, E. F. Fritsch, T. Maniatis, Molecular Cloning: A Laboratory Manual. Mol. Cloning Lab. Man. (1989). J. Sambrook, E. F. Fritsch, T. Maniatis, Molecular Cloning: A Laboratory Manual. Mol. Cloning Lab. Man. (1989).

go back to reference M.M. Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254 (1976)CrossRef M.M. Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254 (1976)CrossRef

go back to reference E.M. Hurt, S.B. Thomas, B. Peng, W.L. Farrar, Reversal of p53 epigenetic silencing in multiple myeloma permits apoptosis by a p53 activator. Cancer Biol Ther 5, 1154–1160 (2006)CrossRef E.M. Hurt, S.B. Thomas, B. Peng, W.L. Farrar, Reversal of p53 epigenetic silencing in multiple myeloma permits apoptosis by a p53 activator. Cancer Biol Ther 5, 1154–1160 (2006)CrossRef

go back to reference J.C. Cheng, D.J. Weisenberger, F.A. Gonzales, G. Liang, G.-L. Xu, Y.-G. Hu, V.E. Marquez, P.A. Jones, Continuous zebularine treatment effectively sustains demethylation in human bladder cancer cells. Mol. Cell. Biol. 24, 1270–1278 (2004)CrossRef J.C. Cheng, D.J. Weisenberger, F.A. Gonzales, G. Liang, G.-L. Xu, Y.-G. Hu, V.E. Marquez, P.A. Jones, Continuous zebularine treatment effectively sustains demethylation in human bladder cancer cells. Mol. Cell. Biol. 24, 1270–1278 (2004)CrossRef

go back to reference M.L. Orta, N. Pastor, E. Burgos-Morón, I. Domínguez, J.M. Calderón-Montaño, C. Huertas Castaño, M. López-Lázaro, T. Helleday, S. Mateos, Zebularine induces replication-dependent double-strand breaks which are preferentially repaired by homologous recombination. DNA Repair 57, 116–124 (2017)CrossRef M.L. Orta, N. Pastor, E. Burgos-Morón, I. Domínguez, J.M. Calderón-Montaño, C. Huertas Castaño, M. López-Lázaro, T. Helleday, S. Mateos, Zebularine induces replication-dependent double-strand breaks which are preferentially repaired by homologous recombination. DNA Repair 57, 116–124 (2017)CrossRef

go back to reference C. Grandjenette, M. Schnekenburger, T. Karius, J. Ghelfi, A. Gaigneaux, E. Henry, M. Dicato, M. Diederich, 5-aza-2′-deoxycytidine-mediated c-myc down-regulation triggers telomere-dependent senescence by regulating human telomerase reverse transcriptase in chronic myeloid leukemia. Neoplasia 6, 511–528 (2014) C. Grandjenette, M. Schnekenburger, T. Karius, J. Ghelfi, A. Gaigneaux, E. Henry, M. Dicato, M. Diederich, 5-aza-2′-deoxycytidine-mediated c-myc down-regulation triggers telomere-dependent senescence by regulating human telomerase reverse transcriptase in chronic myeloid leukemia. Neoplasia 6, 511–528 (2014)

go back to reference C.B. Yoo, R. Valente, C. Congiatu, F. Gavazza, A. Angel, M.A. Siddiqui, P.A. Jones, C. McGuigan, V.E. Marquez, Activation of p16 gene silenced by DNA methylation in cancer cells by phosphoramidate derivatives of 2′-deoxyzebularine. J. Med. Chem. 51, 7593–7601 (2008)CrossRef C.B. Yoo, R. Valente, C. Congiatu, F. Gavazza, A. Angel, M.A. Siddiqui, P.A. Jones, C. McGuigan, V.E. Marquez, Activation of p16 gene silenced by DNA methylation in cancer cells by phosphoramidate derivatives of 2′-deoxyzebularine. J. Med. Chem. 51, 7593–7601 (2008)CrossRef

go back to reference D. Dytfeld, M. Luczak, T. Wrobel, L. Usnarska-Zubkiewicz, K. Brzezniakiewicz, K. Jamroziak, K. Giannopoulos, A. Przybylowicz-Chalecka, B. Ratajczak, J. Czerwinska-Rybak, A. Nowicki, M. Joks, E. Czechowska, M. Zawartko, T. Szczepaniak, N. Grzasko, M. Morawska, M. Bochenek, T. Kubicki, M. Morawska, K. Tusznio, A. Jakubowiak, M. Komarnicki, D. Dytfeld, M. Luczak, T. Wrobel, L. Usnarska-Zubkiewicz, K. Brzezniakiewicz, K. Jamroziak, K. Giannopoulos, A. Przybylowicz-Chalecka, B. Ratajczak, J. Czerwinska-Rybak, A. Nowicki, M. Joks, E. Czechowska, M. Zawartko, T. Szczepaniak, N. Grzasko, M. Morawska, M. Bochenek, T. Kubicki, M. Morawska, K. Tusznio, A. Jakubowiak, M. Komarnicki, Comparative proteomic profiling of refractory/relapsed multiple myeloma reveals biomarkers involved in resistance to bortezomib-based therapy. Oncotarget 7, 56726–56736 (2016)CrossRef D. Dytfeld, M. Luczak, T. Wrobel, L. Usnarska-Zubkiewicz, K. Brzezniakiewicz, K. Jamroziak, K. Giannopoulos, A. Przybylowicz-Chalecka, B. Ratajczak, J. Czerwinska-Rybak, A. Nowicki, M. Joks, E. Czechowska, M. Zawartko, T. Szczepaniak, N. Grzasko, M. Morawska, M. Bochenek, T. Kubicki, M. Morawska, K. Tusznio, A. Jakubowiak, M. Komarnicki, D. Dytfeld, M. Luczak, T. Wrobel, L. Usnarska-Zubkiewicz, K. Brzezniakiewicz, K. Jamroziak, K. Giannopoulos, A. Przybylowicz-Chalecka, B. Ratajczak, J. Czerwinska-Rybak, A. Nowicki, M. Joks, E. Czechowska, M. Zawartko, T. Szczepaniak, N. Grzasko, M. Morawska, M. Bochenek, T. Kubicki, M. Morawska, K. Tusznio, A. Jakubowiak, M. Komarnicki, Comparative proteomic profiling of refractory/relapsed multiple myeloma reveals biomarkers involved in resistance to bortezomib-based therapy. Oncotarget 7, 56726–56736 (2016)CrossRef

go back to reference J.H. Beumer, J.L. Eiseman, R.A. Parise, E. Joseph, J.L. Holleran, J.M. Covey, M.J. Egorin, Pharmacokinetics, metabolism, and oral bioavailability of the DNA methyltransferase inhibitor 5-fluoro-2′-deoxycytidine in mice. Clin. Cancer Res. 12, 7483–7491 (2006) J.H. Beumer, J.L. Eiseman, R.A. Parise, E. Joseph, J.L. Holleran, J.M. Covey, M.J. Egorin, Pharmacokinetics, metabolism, and oral bioavailability of the DNA methyltransferase inhibitor 5-fluoro-2′-deoxycytidine in mice. Clin. Cancer Res. 12, 7483–7491 (2006)

go back to reference M. Billam, M.D. Sobolewski, N.E. Davidson, Effects of a novel DNA methyltransferase inhibitor zebularine on human breast cancer cells. Breast Cancer Res. Treat. 120, 581–592 (2010)CrossRef M. Billam, M.D. Sobolewski, N.E. Davidson, Effects of a novel DNA methyltransferase inhibitor zebularine on human breast cancer cells. Breast Cancer Res. Treat. 120, 581–592 (2010)CrossRef

go back to reference M. Lemaire, L.F. Momparler, M.L. Bernstein, V.E. Marquez, R.L. Momparler, Enhancement of antineoplastic action of 5-aza-2′-deoxycytidine by zebularine on L1210 leukemia. Anti-Cancer Drugs 16, 301–308 (2005)CrossRef M. Lemaire, L.F. Momparler, M.L. Bernstein, V.E. Marquez, R.L. Momparler, Enhancement of antineoplastic action of 5-aza-2′-deoxycytidine by zebularine on L1210 leukemia. Anti-Cancer Drugs 16, 301–308 (2005)CrossRef

go back to reference Z. Zhang, Q. He, Y. Tao, J. Guo, F. Xu, L.-Y. Wu, Y.-S. Zhao, D. Wu, L.-Y. Zhou, J.-Y. Su, L.-X. Song, C. Xiao, X. Li, C.-K. Chang, Decitabine treatment sensitizes tumor cells to T-cell-mediated cytotoxicity in patients with myelodysplastic syndromes. Am. J. Transl. Res. 9, 454–465 (2017)PubMedPubMedCentral Z. Zhang, Q. He, Y. Tao, J. Guo, F. Xu, L.-Y. Wu, Y.-S. Zhao, D. Wu, L.-Y. Zhou, J.-Y. Su, L.-X. Song, C. Xiao, X. Li, C.-K. Chang, Decitabine treatment sensitizes tumor cells to T-cell-mediated cytotoxicity in patients with myelodysplastic syndromes. Am. J. Transl. Res. 9, 454–465 (2017)PubMedPubMedCentral

go back to reference Y. Cui, A. Naz, D.H. Thompson, J. Irudayaraj, Decitabine nanoconjugate sensitizes human glioblastoma cells to temozolomide. Mol. Pharm. 12, 1279–1288 (2015)CrossRef Y. Cui, A. Naz, D.H. Thompson, J. Irudayaraj, Decitabine nanoconjugate sensitizes human glioblastoma cells to temozolomide. Mol. Pharm. 12, 1279–1288 (2015)CrossRef

go back to reference Y. Cao, G.-Q. Qiu, H.-Q. Wu, Z.-L. Wang, Y. Lin, W. Wu, X.-B. Xie, W.-Y. Gu, Decitabine enhances bortezomib treatment in RPMI 8226 multiple myeloma cells. Mol. Med. Rep. 14, 3469–3475 (2016)CrossRef Y. Cao, G.-Q. Qiu, H.-Q. Wu, Z.-L. Wang, Y. Lin, W. Wu, X.-B. Xie, W.-Y. Gu, Decitabine enhances bortezomib treatment in RPMI 8226 multiple myeloma cells. Mol. Med. Rep. 14, 3469–3475 (2016)CrossRef

go back to reference M.B. Heckmann, S. Doroudgar, H.A. Katus, L.H. Lehmann, Cardiovascular adverse events in multiple myeloma patients. J. Thorac. Dis. 10, S4296–S4305 (2018) M.B. Heckmann, S. Doroudgar, H.A. Katus, L.H. Lehmann, Cardiovascular adverse events in multiple myeloma patients. J. Thorac. Dis. 10, S4296–S4305 (2018)

go back to reference C.T. Wallington-Beddoe, M. Sobieraj-Teague, B.J. Kuss, S.M. Pitson, Resistance to proteasome inhibitors and other targeted therapies in myeloma. Br. J. Haematol. 182, 11–28 (2018)CrossRef C.T. Wallington-Beddoe, M. Sobieraj-Teague, B.J. Kuss, S.M. Pitson, Resistance to proteasome inhibitors and other targeted therapies in myeloma. Br. J. Haematol. 182, 11–28 (2018)CrossRef

go back to reference D.J.P.M. Stumpel, D. Schotte, P. Schneider, L. Seslija, R.X. de Menezes, V.E. Marquez, R. Pieters, M.L. den Boer, R.W. Stam, Hypermethylation of specific microRNA genes in MLL-rearranged infant acute lymphoblastic leukemia: major matters at a micro scale. Leukemia 25, 429–439 (2011)CrossRef D.J.P.M. Stumpel, D. Schotte, P. Schneider, L. Seslija, R.X. de Menezes, V.E. Marquez, R. Pieters, M.L. den Boer, R.W. Stam, Hypermethylation of specific microRNA genes in MLL-rearranged infant acute lymphoblastic leukemia: major matters at a micro scale. Leukemia 25, 429–439 (2011)CrossRef

go back to reference M. Zauri, G. Berridge, M.-L. Thézénas, K.M. Pugh, R. Goldin, B.M. Kessler, S. Kriaucionis, CDA directs metabolism of epigenetic nucleosides revealing a therapeutic window in cancer. Nature 524, 114–118 (2015)CrossRef M. Zauri, G. Berridge, M.-L. Thézénas, K.M. Pugh, R. Goldin, B.M. Kessler, S. Kriaucionis, CDA directs metabolism of epigenetic nucleosides revealing a therapeutic window in cancer. Nature 524, 114–118 (2015)CrossRef

go back to reference R.Z. Mahfouz, A. Jankowska, Q. Ebrahem, X. Gu, V. Visconte, A. Tabarroki, P. Terse, J. Covey, K. Chan, Y. Ling, K.J. Engelke, M.A. Sekeres, R. Tiu, J. Maciejewski, T. Radivoyevitch, Y. Saunthararajah, Increased CDA expression/activity in males contributes to decreased cytidine analog half-life and likely contributes to worse outcomes with 5-azacytidine or decitabine therapy. Clin. Cancer Res. 19, 938–948 (2013) R.Z. Mahfouz, A. Jankowska, Q. Ebrahem, X. Gu, V. Visconte, A. Tabarroki, P. Terse, J. Covey, K. Chan, Y. Ling, K.J. Engelke, M.A. Sekeres, R. Tiu, J. Maciejewski, T. Radivoyevitch, Y. Saunthararajah, Increased CDA expression/activity in males contributes to decreased cytidine analog half-life and likely contributes to worse outcomes with 5-azacytidine or decitabine therapy. Clin. Cancer Res. 19, 938–948 (2013)

go back to reference T. Neff, C.A. Blau, Forced expression of cytidine deaminase confers resistance to cytosine arabinoside and gemcitabine. Exp. Hematol. 24, 1340–1346 (1996)PubMed T. Neff, C.A. Blau, Forced expression of cytidine deaminase confers resistance to cytosine arabinoside and gemcitabine. Exp. Hematol. 24, 1340–1346 (1996)PubMed

go back to reference H. Guo, N. Rao, Q. Xu, H. Guo, Origin of tight binding of a near-perfect transition-state analogue by cytidine deaminase: Implications for enzyme catalysis. J. Am. Chem. Soc. 127, 3191–3197 (2005)CrossRef H. Guo, N. Rao, Q. Xu, H. Guo, Origin of tight binding of a near-perfect transition-state analogue by cytidine deaminase: Implications for enzyme catalysis. J. Am. Chem. Soc. 127, 3191–3197 (2005)CrossRef

go back to reference P.L. Greenberg, E. Attar, J.M. Bennett, C.D. Bloomfield, C.M. De Castro, H.J. Deeg, J.M. Foran, K. Gaensler, G. Garcia-Manero, S.D. Gore, D. Head, R. Komrokji, L.J. Maness, M. Millenson, S.D. Nimer, M.R. O’Donnell, M.A. Schroeder, P.J. Shami, R.M. Stone, J.E. Thompson, P. Westervelt, National Comprehensive Cancer Network, NCCN clinical practice guidelines in oncology: myelodysplastic syndromes. J. Natl. Compr. Cancer Netw. JNCCN 9, 30–56 (2011)CrossRef P.L. Greenberg, E. Attar, J.M. Bennett, C.D. Bloomfield, C.M. De Castro, H.J. Deeg, J.M. Foran, K. Gaensler, G. Garcia-Manero, S.D. Gore, D. Head, R. Komrokji, L.J. Maness, M. Millenson, S.D. Nimer, M.R. O’Donnell, M.A. Schroeder, P.J. Shami, R.M. Stone, J.E. Thompson, P. Westervelt, National Comprehensive Cancer Network, NCCN clinical practice guidelines in oncology: myelodysplastic syndromes. J. Natl. Compr. Cancer Netw. JNCCN 9, 30–56 (2011)CrossRef