Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Reversine: A Synthetic Purine with a Dual Activity as a Cell Dedifferentiating Agent and a Selective Anticancer Drug

Author(s): Marco Piccoli, Andrea Ghiroldi, Michelle M. Monasky, Federica Cirillo, Giuseppe Ciconte, Carlo Pappone and Luigi Anastasia*

Volume 27, Issue 21, 2020

Page: [3448 - 3462] Pages: 15

DOI: 10.2174/0929867326666190103120725

Price: $65

Abstract

The development of new therapeutic applications for adult and embryonic stem cells has dominated regenerative medicine and tissue engineering for several decades. However, since 2006, induced Pluripotent Stem Cells (iPSCs) have taken center stage in the field, as they promised to overcome several limitations of the other stem cell types. Nonetheless, other promising approaches for adult cell reprogramming have been attempted over the years, even before the generation of iPSCs. In particular, two years before the discovery of iPSCs, the possibility of synthesizing libraries of large organic compounds, as well as the development of high-throughput screenings to quickly test their biological activity, enabled the identification of a 2,6-disubstituted purine, named reversine, which was shown to be able to reprogram adult cells to a progenitor-like state. Since its discovery, the effect of reversine has been confirmed on different cell types, and several studies on its mechanism of action have revealed its central role in inhibitory activity on several kinases implicated in cell cycle regulation and cytokinesis. These key features, together with its chemical nature, suggested a possible use of the molecule as an anti-cancer drug. Remarkably, reversine exhibited potent cytotoxic activity against several tumor cell lines in vitro and a significant effect in decreasing tumor progression and metastatization in vivo. Thus, 15 years since its discovery, this review aims at critically summarizing the current knowledge to clarify the dual role of reversine as a dedifferentiating agent and anti-cancer drug.

Keywords: Reversine, dedifferentiation, reprogramming, repositioning, cancer, anti-tumor drugs.

« Previous Next »
[1]
Hall, W.S.; Eubank, M.D. The regeneration of the blood. J. Exp. Med., 1896, 1(4), 656-676.
[http://dx.doi.org/10.1084/jem.1.4.656] [PMID: 19866819]
[2]
Alison, M.R.; Poulsom, R.; Forbes, S.; Wright, N.A. An introduction to stem cells. J. Pathol., 2002, 197(4), 419-423.
[http://dx.doi.org/10.1002/path.1187] [PMID: 12115858]
[3]
Blau, H.M.; Brazelton, T.R.; Weimann, J.M. The evolving concept of a stem cell: entity or function? Cell, 2001, 105(7), 829-841.
[http://dx.doi.org/10.1016/S0092-8674(01)00409-3] [PMID: 11439179]
[4]
Boese, A.C.; Le, Q.E.; Pham, D.; Hamblin, M.H.; Lee, J.P. Neural stem cell therapy for subacute and chronic ischemic stroke. Stem Cell Res. Ther., 2018, 9(1), 154.
[http://dx.doi.org/10.1186/s13287-018-0913-2] [PMID: 29895321]
[5]
Iansante, V.; Chandrashekran, A.; Dhawan, A. Cell-based liver therapies: past, present and future. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2018, 373(1750), 20170229
[http://dx.doi.org/10.1098/rstb.2017.0229]
[6]
Menasché, P. Cell therapy trials for heart regeneration - lessons learned and future directions. Nat. Rev. Cardiol., 2018, 15(11), 659-671.
[http://dx.doi.org/10.1038/s41569-018-0013-0] [PMID: 29743563]
[7]
Murray, I.R.; West, C.C.; Hardy, W.R.; James, A.W.; Park, T.S.; Nguyen, A.; Tawonsawatruk, T.; Lazzari, L.; Soo, C.; Péault, B. Natural history of mesenchymal stem cells, from vessel walls to culture vessels. Cell. Mol. Life Sci., 2014, 71(8), 1353-1374.
[http://dx.doi.org/10.1007/s00018-013-1462-6] [PMID: 24158496]
[8]
Smith, S.; Neaves, W.; Teitelbaum, S. Adult versus embryonic stem cells: treatments. Science, 2007, 316(5830), 1422-1423.
[http://dx.doi.org/10.1126/science.316.5830.1422b] [PMID: 17556566]
[9]
Bianco, P. “Mesenchymal” stem cells. Annu. Rev. Cell Dev. Biol., 2014, 30, 677-704.
[http://dx.doi.org/10.1146/annurev-cellbio-100913-013132] [PMID: 25150008]
[10]
Cagliani, J.; Grande, D.; Molmenti, E.P.; Miller, E.J.; Rilo, H.L.R. Immunomodulation by mesenchymal stromal cells and their clinical applications. J Stem Cell Regen Biol, 2017, 3(2)
[http://dx.doi.org/10.15436/2471-0598.17.022] [PMID: 29104965]
[11]
Agarwal, S. Cellular reprogramming. Methods Enzymol., 2006, 420, 265-283.
[http://dx.doi.org/10.1016/S0076-6879(06)20012-0] [PMID: 17161701]
[12]
Cowan, C.A.; Atienza, J.; Melton, D.A.; Eggan, K. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science, 2005, 309(5739), 1369-1373.
[http://dx.doi.org/10.1126/science.1116447] [PMID: 16123299]
[13]
Hochedlinger, K.; Jaenisch, R. Nuclear reprogramming and pluripotency. Nature, 2006, 441(7097), 1061-1067.
[http://dx.doi.org/10.1038/nature04955] [PMID: 16810240]
[14]
Tada, M.; Takahama, Y.; Abe, K.; Nakatsuji, N.; Tada, T. Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr. Biol., 2001, 11(19), 1553-1558.
[http://dx.doi.org/10.1016/S0960-9822(01)00459-6] [PMID: 11591326]
[15]
Wilmut, I.; Schnieke, A.E.; McWhir, J.; Kind, A.J.; Campbell, K.H. Viable offspring derived from fetal and adult mammalian cells. Nature, 1997, 385(6619), 810-813.
[http://dx.doi.org/10.1038/385810a0] [PMID: 9039911]
[16]
Takahashi, K.; Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006, 126(4), 663-676.
[http://dx.doi.org/10.1016/j.cell.2006.07.024] [PMID: 16904174]
[17]
Ding, S.; Schultz, P.G. A role for chemistry in stem cell biology. Nat. Biotechnol., 2004, 22(7), 833-840.
[http://dx.doi.org/10.1038/nbt987] [PMID: 15229546]
[18]
Bain, G.; Kitchens, D.; Yao, M.; Huettner, J.E.; Gottlieb, D.I. Embryonic stem cells express neuronal properties in vitro. Dev. Biol., 1995, 168(2), 342-357.
[http://dx.doi.org/10.1006/dbio.1995.1085] [PMID: 7729574]
[19]
Burlacu, A. Can 5-azacytidine convert the adult stem cells into cardiomyocytes? A brief overview. Arch. Physiol. Biochem., 2006, 112(4-5), 260-264.
[http://dx.doi.org/10.1080/13813450601094631] [PMID: 17178600]
[20]
Xu, Y.; Shi, Y.; Ding, S. A chemical approach to stem-cell biology and regenerative medicine. Nature, 2008, 453(7193), 338-344.
[http://dx.doi.org/10.1038/nature07042] [PMID: 18480815]
[21]
Rosania, G.R.; Chang, Y.T.; Perez, O.; Sutherlin, D.; Dong, H.; Lockhart, D.J.; Schultz, P.G. Myoseverin, a microtubule-binding molecule with novel cellular effects. Nat. Biotechnol., 2000, 18(3), 304-308.
[http://dx.doi.org/10.1038/73753] [PMID: 10700146]
[22]
Duckmanton, A.; Kumar, A.; Chang, Y.T.; Brockes, J.P. A single-cell analysis of myogenic dedifferentiation induced by small molecules. Chem. Biol., 2005, 12(10), 1117-1126.
[http://dx.doi.org/10.1016/j.chembiol.2005.07.011] [PMID: 16242654]
[23]
Anastasia, L.; Sampaolesi, M.; Papini, N.; Oleari, D.; Lamorte, G.; Tringali, C.; Monti, E.; Galli, D.; Tettamanti, G.; Cossu, G.; Venerando, B. Reversine-treated fibroblasts acquire myogenic competence in vitro and in regenerating skeletal muscle. Cell Death Differ., 2006, 13(12), 2042-2051.
[http://dx.doi.org/10.1038/sj.cdd.4401958] [PMID: 16729034]
[24]
Chen, S.; Zhang, Q.; Wu, X.; Schultz, P.G.; Ding, S. Dedifferentiation of lineage-committed cells by a small molecule. J. Am. Chem. Soc., 2004, 126(2), 410-411.
[http://dx.doi.org/10.1021/ja037390k] [PMID: 14719906]
[25]
Gey, C.; Giannis, A. Small molecules, big plans--can low-molecular-weight compounds control human regeneration? Angew. Chem. Int. Ed. Engl., 2004, 43(31), 3998-4000.
[http://dx.doi.org/10.1002/anie.200460346] [PMID: 15300685]
[26]
Anastasia, L.; Piccoli, M.; Garatti, A.; Conforti, E.; Scaringi, R.; Bergante, S.; Castelvecchio, S.; Venerando, B.; Menicanti, L.; Tettamanti, G. Cell reprogramming: a new chemical approach to stem cell biology and tissue regeneration. Curr. Pharm. Biotechnol., 2011, 12(2), 146-150.
[http://dx.doi.org/10.2174/138920111794295828] [PMID: 21044013]
[27]
Barker, R.A.; Götz, M.; Parmar, M. New approaches for brain repair-from rescue to reprogramming. Nature, 2018, 557(7705), 329-334.
[http://dx.doi.org/10.1038/s41586-018-0087-1] [PMID: 29769670]
[28]
Ghiroldi, A.; Piccoli, M.; Ciconte, G.; Pappone, C.; Anastasia, L. Regenerating the human heart: direct reprogramming strategies and their current limitations. Basic Res. Cardiol., 2017, 112(6), 68.
[http://dx.doi.org/10.1007/s00395-017-0655-9] [PMID: 29079873]
[29]
Papaccio, F.; Paino, F.; Regad, T.; Papaccio, G.; Desiderio, V.; Tirino, V. Concise review: Cancer cells, cancer stem cells, and mesenchymal stem cells: Influence in cancer development. Stem Cells Transl. Med., 2017, 6(12), 2115-2125.
[http://dx.doi.org/10.1002/sctm.17-0138] [PMID: 29072369]
[30]
Yamada, Y.; Haga, H.; Yamada, Y. Concise review: dedifferentiation meets cancer development: proof of concept for epigenetic cancer. Stem Cells Transl. Med., 2014, 3(10), 1182-1187.
[http://dx.doi.org/10.5966/sctm.2014-0090] [PMID: 25122691]
[31]
Visvader, J.E. Cells of origin in cancer. Nature, 2011, 469(7330), 314-322.
[http://dx.doi.org/10.1038/nature09781] [PMID: 21248838]
[32]
Friedmann-Morvinski, D.; Verma, I.M. Dedifferentiation and reprogramming: origins of cancer stem cells. EMBO Rep., 2014, 15(3), 244-253.
[http://dx.doi.org/10.1002/embr.201338254] [PMID: 24531722]
[33]
Hsieh, T.C.; Traganos, F.; Darzynkiewicz, Z.; Wu, J.M. The 2,6-disubstituted purine reversine induces growth arrest and polyploidy in human cancer cells. Int. J. Oncol., 2007, 31(6), 1293-1300.
[http://dx.doi.org/10.3892/ijo.31.6.1293] [PMID: 17982654]
[34]
Kim, W.H.; Shen, H.; Jung, D.W.; Williams, D.R. Some leopards can change their spots: potential repositioning of stem cell reprogramming compounds as anti-cancer agents. Cell Biol. Toxicol., 2016, 32(3), 157-168.
[http://dx.doi.org/10.1007/s10565-016-9333-1] [PMID: 27156576]
[35]
Brockes, J.P.; Kumar, A. Plasticity and reprogramming of differentiated cells in amphibian regeneration. Nat. Rev. Mol. Cell Biol., 2002, 3(8), 566-574.
[http://dx.doi.org/10.1038/nrm881] [PMID: 12154368]
[36]
Poss, K.D.; Wilson, L.G.; Keating, M.T. Heart regeneration in zebrafish. Science, 2002, 298(5601), 2188-2190.
[http://dx.doi.org/10.1126/science.1077857] [PMID: 12481136]
[37]
Grafi, G. The complexity of cellular dedifferentiation: implications for regenerative medicine. Trends Biotechnol., 2009, 27(6), 329-332.
[http://dx.doi.org/10.1016/j.tibtech.2009.02.007] [PMID: 19395104]
[38]
Brockes, J.P.; Kumar, A. Comparative aspects of animal regeneration. Annu. Rev. Cell Dev. Biol., 2008, 24, 525-549.
[http://dx.doi.org/10.1146/annurev.cellbio.24.110707.175336] [PMID: 18598212]
[39]
Ding, S.; Gray, N.S.; Wu, X.; Ding, Q.; Schultz, P.G. A combinatorial scaffold approach toward kinase-directed heterocycle libraries. J. Am. Chem. Soc., 2002, 124(8), 1594-1596.
[http://dx.doi.org/10.1021/ja0170302] [PMID: 11853431]
[40]
Kim, S.; Rosania, G.R.; Chang, Y.T. Dedifferentiation? What’s next? Mol. Interv., 2004, 4(2), 83-85.
[http://dx.doi.org/10.1124/mi.4.2.5] [PMID: 15087481]
[41]
Fux, C.; Mitta, B.; Kramer, B.P.; Fussenegger, M. Dual-regulated expression of C/EBP-alpha and BMP-2 enables differential differentiation of C2C12 cells into adipocytes and osteoblasts. Nucleic Acids Res., 2004, 32(1), e1
[http://dx.doi.org/10.1093/nar/gnh001] [PMID: 14704358]
[42]
Holst, D.; Luquet, S.; Kristiansen, K.; Grimaldi, P.A. Roles of peroxisome proliferator-activated receptors delta and gamma in myoblast transdifferentiation. Exp. Cell Res., 2003, 288(1), 168-176.
[http://dx.doi.org/10.1016/S0014-4827(03)00179-4] [PMID: 12878168]
[43]
Katagiri, T.; Yamaguchi, A.; Komaki, M.; Abe, E.; Takahashi, N.; Ikeda, T.; Rosen, V.; Wozney, J.M.; Fujisawa-Sehara, A.; Suda, T. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J. Cell Biol., 1994, 127(6 Pt 1), 1755-1766.
[http://dx.doi.org/10.1083/jcb.127.6.1755] [PMID: 7798324]
[44]
Chen, S.; Takanashi, S.; Zhang, Q.; Xiong, W.; Zhu, S.; Peters, E.C.; Ding, S.; Schultz, P.G. Reversine increases the plasticity of lineage-committed mammalian cells. Proc. Natl. Acad. Sci. USA, 2007, 104(25), 10482-10487.
[http://dx.doi.org/10.1073/pnas.0704360104] [PMID: 17566101]
[45]
Kolch, W. Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat. Rev. Mol. Cell Biol., 2005, 6(11), 827-837.
[http://dx.doi.org/10.1038/nrm1743] [PMID: 16227978]
[46]
Ait-Si-Ali, S.; Carlisi, D.; Ramirez, S.; Upegui-Gonzalez, L.C.; Duquet, A.; Robin, P.; Rudkin, B.; Harel-Bellan, A.; Trouche, D. Phosphorylation by p44 MAP Kinase/ERK1 stimulates CBP histone acetyl transferase activity in vitro. Biochem. Biophys. Res. Commun., 1999, 262(1), 157-162.
[http://dx.doi.org/10.1006/bbrc.1999.1132] [PMID: 10448085]
[47]
Kawasaki, H.; Schiltz, L.; Chiu, R.; Itakura, K.; Taira, K.; Nakatani, Y.; Yokoyama, K.K. ATF-2 has intrinsic histone acetyltransferase activity which is modulated by phosphorylation. Nature, 2000, 405(6783), 195-200.
[http://dx.doi.org/10.1038/35012097] [PMID: 10821277]
[48]
Shan, S.W.; Tang, M.K.; Chow, P.H.; Maroto, M.; Cai, D.Q.; Lee, K.K. Induction of growth arrest and polycomb gene expression by reversine allows C2C12 cells to be reprogrammed to various differentiated cell types. Proteomics, 2007, 7(23), 4303-4316.
[http://dx.doi.org/10.1002/pmic.200700636] [PMID: 17973295]
[49]
Chou, R.H.; Chiu, L.; Yu, Y.L.; Shyu, W.C. The potential roles of EZH2 in regenerative medicine. Cell Transplant., 2015, 24(3), 313-317.
[http://dx.doi.org/10.3727/096368915X686823] [PMID: 25647295]
[50]
Simon, J.A.; Kingston, R.E. Mechanisms of polycomb gene silencing: knowns and unknowns. Nat. Rev. Mol. Cell Biol., 2009, 10(10), 697-708.
[http://dx.doi.org/10.1038/nrm2763] [PMID: 19738629]
[51]
Fania, C.; Anastasia, L.; Vasso, M.; Papini, N.; Capitanio, D.; Venerando, B.; Gelfi, C. Proteomic signature of reversine-treated murine fibroblasts by 2-D difference gel electrophoresis and MS: possible associations with cell signalling networks. Electrophoresis, 2009, 30(12), 2193-2206.
[http://dx.doi.org/10.1002/elps.200800800] [PMID: 19582720]
[52]
Thomas, S.; Bonchev, D. A survey of current software for network analysis in molecular biology. Hum. Genomics, 2010, 4(5), 353-360.
[http://dx.doi.org/10.1186/1479-7364-4-5-353] [PMID: 20650822]
[53]
Lee, E.K.; Bae, G.U.; You, J.S.; Lee, J.C.; Jeon, Y.J.; Park, J.W.; Park, J.H.; Ahn, S.H.; Kim, Y.K.; Choi, W.S.; Kang, J-S.; Han, G.; Han, J-W. Reversine increases the plasticity of lineage-committed cells toward neuroectodermal lineage. J. Biol. Chem., 2009, 284(5), 2891-2901.
[http://dx.doi.org/10.1074/jbc.M804055200] [PMID: 19015271]
[54]
Saraiya, M.; Nasser, R.; Zeng, Y.; Addya, S.; Ponnappan, R.K.; Fortina, P.; Anderson, D.G.; Albert, T.J.; Shapiro, I.M.; Risbud, M.V. Reversine enhances generation of progenitor-like cells by dedifferentiation of annulus fibrosus cells. Tissue Eng. Part A, 2010, 16(4), 1443-1455.
[http://dx.doi.org/10.1089/ten.tea.2009.0343] [PMID: 19947906]
[55]
Chen, J.F.; Mandel, E.M.; Thomson, J.M.; Wu, Q.; Callis, T.E.; Hammond, S.M.; Conlon, F.L.; Wang, D.Z. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat. Genet., 2006, 38(2), 228-233.
[http://dx.doi.org/10.1038/ng1725] [PMID: 16380711]
[56]
Kim, M.; Yi, S.A.; Lee, H.; Bang, S.Y.; Park, E.K.; Lee, M.G.; Nam, K.H.; Yoo, J.H.; Lee, D.H.; Ryu, H.W.; Kwon, S.H.; Han, J.W. Reversine induces multipotency of lineage-committed cells through epigenetic silencing of miR-133a. Biochem. Biophys. Res. Commun., 2014, 445(1), 255-262.
[http://dx.doi.org/10.1016/j.bbrc.2014.02.002] [PMID: 24513286]
[57]
D’Alise, A.M.; Amabile, G.; Iovino, M.; Di Giorgio, F.P.; Bartiromo, M.; Sessa, F.; Villa, F.; Musacchio, A.; Cortese, R. Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells. Mol. Cancer Ther., 2008, 7(5), 1140-1149.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-2051] [PMID: 18483302]
[58]
Amabile, G.; D’Alise, A.M.; Iovino, M.; Jones, P.; Santaguida, S.; Musacchio, A.; Taylor, S.; Cortese, R. The Aurora B kinase activity is required for the maintenance of the differentiated state of murine myoblasts. Cell Death Differ., 2009, 16(2), 321-330.
[http://dx.doi.org/10.1038/cdd.2008.156] [PMID: 18974773]
[59]
Giet, R.; Glover, D.M. Drosophila aurora B kinase is required for histone H3 phosphorylation and condensin recruitment during chromosome condensation and to organize the central spindle during cytokinesis. J. Cell Biol., 2001, 152(4), 669-682.
[http://dx.doi.org/10.1083/jcb.152.4.669] [PMID: 11266459]
[60]
Qu, G.; von Schroeder, H.P. Preliminary evidence for the dedifferentiation of RAW 264.7 cells into mesenchymal progenitor-like cells by a purine analog. Tissue Eng. Part A, 2012, 18(17-18), 1890-1901.
[http://dx.doi.org/10.1089/ten.tea.2010.0692] [PMID: 22519969]
[61]
Li, X.; Guo, Y.; Yao, Y.; Hua, J.; Ma, Y.; Liu, C.; Guan, W. Reversine increases the plasticity of long-term cryopreserved fibroblasts to multipotent progenitor cells through activation of Oct4. Int. J. Biol. Sci., 2016, 12(1), 53-62.
[http://dx.doi.org/10.7150/ijbs.12199] [PMID: 26722217]
[62]
Conforti, E.; Arrigoni, E.; Piccoli, M.; Lopa, S.; de Girolamo, L.; Ibatici, A.; Di Matteo, A.; Tettamanti, G.; Brini, A.T.; Anastasia, L. Reversine increases multipotent human mesenchymal cells differentiation potential. J. Biol. Regul. Homeost. Agents, 2011, 25(Suppl. 2), S25-S33.
[PMID: 22051168]
[63]
Lv, X.; Zhu, H.; Bai, Y.; Chu, Z.; Hu, Y.; Cao, H.; Liu, C.; He, X.; Peng, S.; Gao, Z.; Yang, C.; Hua, J. Reversine promotes porcine muscle derived stem cells (PMDSCs) differentiation into female germ-like cells. J. Cell. Biochem., 2012, 113(12), 3629-3642.
[http://dx.doi.org/10.1002/jcb.24296] [PMID: 22821411]
[64]
Pikir, B.S.; Susilowati, H.; Hendrianto, E.; Abdulrantam, F. Reversin increase the plasticity of bone marrow-derived mesenchymal stem cell for generation of cardiomyocyte in vitro. Acta Med. Indones., 2012, 44(1), 23-27.
[PMID: 22451181]
[65]
Soltani, L.; Rahmani, H.R.; Daliri Joupari, M.; Ghaneialvar, H.; Mahdavi, A.H.; Shamsara, M. Ovine fetal mesenchymal stem cell differentiation to cardiomyocytes, effects of co-culture, role of small molecules; reversine and 5-azacytidine. Cell Biochem. Funct., 2016, 34(4), 250-261.
[http://dx.doi.org/10.1002/cbf.3187] [PMID: 27121349]
[66]
Jung, D.W.; Williams, D.R. Novel chemically defined approach to produce multipotent cells from terminally differentiated tissue syncytia. ACS Chem. Biol., 2011, 6(6), 553-562.
[http://dx.doi.org/10.1021/cb2000154] [PMID: 21322636]
[67]
Kim, W.H.; Jung, D.W.; Kim, J.; Im, S.H.; Hwang, S.Y.; Williams, D.R. Small molecules that recapitulate the early steps of urodele amphibian limb regeneration and confer multipotency. ACS Chem. Biol., 2012, 7(4), 732-743.
[http://dx.doi.org/10.1021/cb200532v] [PMID: 22270490]
[68]
Sharma, S.; Mehndiratta, S.; Kumar, S.; Singh, J.; Bedi, P.M.; Nepali, K. Purine analogues as kinase inhibitors: a review. Recent Patents Anticancer Drug Discov., 2015, 10(3), 308-341.
[http://dx.doi.org/10.2174/1574892810666150617112230] [PMID: 26081925]
[69]
Lin, J.; Haffner, M.C.; Zhang, Y.; Lee, B.H.; Brennen, W.N.; Britton, J.; Kachhap, S.K.; Shim, J.S.; Liu, J.O.; Nelson, W.G.; Yegnasubramanian, S.; Carducci, M.A. Disulfiram is a DNA demethylating agent and inhibits prostate cancer cell growth. Prostate, 2011, 71(4), 333-343.
[http://dx.doi.org/10.1002/pros.21247] [PMID: 20809552]
[70]
Voelker, R. International group seeks to dispel incontinence “taboo”. JAMA, 1998, 280(11), 951-953.
[http://dx.doi.org/10.1001/jama.280.11.951] [PMID: 9749464]
[71]
Mazor, M.; Kawano, Y.; Zhu, H.; Waxman, J.; Kypta, R.M. Inhibition of glycogen synthase kinase-3 represses androgen receptor activity and prostate cancer cell growth. Oncogene, 2004, 23(47), 7882-7892.
[http://dx.doi.org/10.1038/sj.onc.1208068] [PMID: 15361837]
[72]
De Souza, C.; Chatterji, B.P. HDAC inhibitors as novel anti-cancer therapeutics. Recent Patents Anticancer Drug Discov., 2015, 10(2), 145-162.
[http://dx.doi.org/10.2174/1574892810666150317144511] [PMID: 25782916]
[73]
Santaguida, S.; Tighe, A.; D’Alise, A.M.; Taylor, S.S.; Musacchio, A. Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine. J. Cell Biol., 2010, 190(1), 73-87.
[http://dx.doi.org/10.1083/jcb.201001036] [PMID: 20624901]
[74]
Libouban, M.A.A.; de Roos, J.A.D.M.; Uitdehaag, J.C.M.; Willemsen-Seegers, N.; Mainardi, S.; Dylus, J.; de Man, J.; Tops, B.; Meijerink, J.P.P.; Storchová, Z.; Buijsman, R.C.; Medema, R.H.; Zaman, G.J.R. Stable aneuploid tumors cells are more sensitive to TTK inhibition than chromosomally unstable cell lines. Oncotarget, 2017, 8(24), 38309-38325.
[http://dx.doi.org/10.18632/oncotarget.16213] [PMID: 28415765]
[75]
Hiruma, Y.; Koch, A.; Dharadhar, S.; Joosten, R.P.; Perrakis, A. Structural basis of reversine selectivity in inhibiting Mps1 more potently than aurora B kinase. Proteins, 2016, 84(12), 1761-1766.
[http://dx.doi.org/10.1002/prot.25174] [PMID: 27699881]
[76]
Hua, S.C.; Chang, T.C.; Chen, H.R.; Lu, C.H.; Liu, Y.W.; Chen, S.H.; Yu, H.I.; Chang, Y.P.; Lee, Y.R. Reversine, a 2,6-disubstituted purine, as an anti-cancer agent in differentiated and undifferentiated thyroid cancer cells. Pharm. Res., 2012, 29(7), 1990-2005.
[http://dx.doi.org/10.1007/s11095-012-0727-3] [PMID: 22477067]
[77]
Qin, H.X.; Yang, J.; Cui, H.K.; Li, S.P.; Zhang, W.; Ding, X.L.; Xia, Y.H. Synergistic antitumor activity of reversine combined with aspirin in cervical carcinoma in vitro and in vivo. Cytotechnology, 2013, 65(4), 643-653.
[http://dx.doi.org/10.1007/s10616-012-9520-8] [PMID: 23475158]
[78]
Kuo, C.H.; Lu, Y.C.; Tseng, Y.S.; Shi, C.S.; Chen, S.H.; Chen, P.T.; Wu, F.L.; Chang, Y.P.; Lee, Y.R. Reversine induces cell cycle arrest, polyploidy, and apoptosis in human breast cancer cells. Breast Cancer, 2014, 21(3), 358-369.
[http://dx.doi.org/10.1007/s12282-012-0400-z] [PMID: 22926505]
[79]
Rodrigues Alves, A.P.; Machado-Neto, J.A.; Scheucher, P.S.; Paiva, H.H.; Simões, B.P.; Rego, E.M.; Traina, F. Reversine triggers mitotic catastrophe and apoptosis in K562 cells. Leuk. Res., 2016, 48, 26-31.
[http://dx.doi.org/10.1016/j.leukres.2016.06.011] [PMID: 27447890]
[80]
Cheng, L.; Wang, H.; Guo, K.; Wang, Z.; Zhang, Z.; Shen, C.; Chen, L.; Lin, J. Reversine, a substituted purine, exerts an inhibitive effect on human renal carcinoma cells via induction of cell apoptosis and polyploidy. OncoTargets Ther., 2018, 11, 1025-1035.
[http://dx.doi.org/10.2147/OTT.S158198] [PMID: 29520153]
[81]
Lu, Y.C.; Lee, Y.R.; Liao, J.D.; Lin, C.Y.; Chen, Y.Y.; Chen, P.T.; Tseng, Y.S. Reversine induced multinucleated cells, cell apoptosis and autophagy in human non-small cell lung cancer cells. PLoS One, 2016, 11(7), e0158587
[http://dx.doi.org/10.1371/journal.pone.0158587] [PMID: 27385117]
[82]
Piccoli, M.; Palazzolo, G.; Conforti, E.; Lamorte, G.; Papini, N.; Creo, P.; Fania, C.; Scaringi, R.; Bergante, S.; Tringali, C.; Roncoroni, L.; Mazzoleni, S.; Doneda, L.; Galli, R.; Venerando, B.; Tettamanti, G.; Gelfi, C.; Anastasia, L. The synthetic purine reversine selectively induces cell death of cancer cells. J. Cell. Biochem., 2012, 113(10), 3207-3217.
[http://dx.doi.org/10.1002/jcb.24197] [PMID: 22615034]
[83]
Fang, C.Y.; Chen, J.S.; Chang, S.K.; Shen, C.H. Reversine induces autophagic cell death through the AMP-activated protein kinase pathway in urothelial carcinoma cells. Anticancer Drugs, 2018, 29(1), 29-39.
[http://dx.doi.org/10.1097/CAD.0000000000000563] [PMID: 28984683]
[84]
Lee, Y.R.; Wu, W.C.; Ji, W.T.; Chen, J.Y.; Cheng, Y.P.; Chiang, M.K.; Chen, H.R. Reversine suppresses oral squamous cell carcinoma via cell cycle arrest and concomitantly apoptosis and autophagy. J. Biomed. Sci., 2012, 19, 9.
[http://dx.doi.org/10.1186/1423-0127-19-9] [PMID: 22283874]
[85]
Lu, C.H.; Liu, Y.W.; Hua, S.C.; Yu, H.I.; Chang, Y.P.; Lee, Y.R. Autophagy induction of reversine on human follicular thyroid cancer cells. Biomed. Pharmacother., 2012, 66(8), 642-647.
[http://dx.doi.org/10.1016/j.biopha.2012.08.001] [PMID: 23089471]
[86]
Gozuacik, D.; Kimchi, A. Autophagy as a cell death and tumor suppressor mechanism. Oncogene, 2004, 23(16), 2891-2906.
[http://dx.doi.org/10.1038/sj.onc.1207521] [PMID: 15077152]
[87]
Lorin, S.; Hamaï, A.; Mehrpour, M.; Codogno, P. Autophagy regulation and its role in cancer. Semin. Cancer Biol., 2013, 23(5), 361-379.
[http://dx.doi.org/10.1016/j.semcancer.2013.06.007] [PMID: 23811268]
[88]
Paquette, M.; El-Houjeiri, L.; Pause, A. mTOR pathways in cancer and autophagy. Cancers (Basel), 2018, 10(1), E18
[http://dx.doi.org/10.3390/cancers10010018] [PMID: 29329237]
[89]
Zhang, S.; Li, J.; Zhou, G.; Mu, D.; Yan, J.; Xing, J.; Yao, Z.; Sheng, H.; Li, D.; Lv, C.; Sun, B.; Hong, Q.; Guo, H. Aurora-A regulates autophagy through the Akt pathway in human prostate cancer. Cancer Biomark., 2017, 19(1), 27-34.
[http://dx.doi.org/10.3233/CBM-160238] [PMID: 28269749]
[90]
Bijian, K.; Lougheed, C.; Su, J.; Xu, B.; Yu, H.; Wu, J.H.; Riccio, K.; Alaoui-Jamali, M.A. Targeting focal adhesion turnover in invasive breast cancer cells by the purine derivative reversine. Br. J. Cancer, 2013, 109(11), 2810-2818.
[http://dx.doi.org/10.1038/bjc.2013.675] [PMID: 24169345]
[91]
Romain, C.V.; Paul, P.; Lee, S.; Qiao, J.; Chung, D.H. Targeting aurora kinase A inhibits hypoxia-mediated neuroblastoma cell tumorigenesis. Anticancer Res., 2014, 34(5), 2269-2274.
[PMID: 24778030]
[92]
McMillin, D.W.; Delmore, J.; Weisberg, E.; Negri, J.M.; Geer, D.C.; Klippel, S.; Mitsiades, N.; Schlossman, R.L.; Munshi, N.C.; Kung, A.L.; Griffin, J.D.; Richardson, P.G.; Anderson, K.C.; Mitsiades, C.S. Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity. Nat. Med., 2010, 16(4), 483-489.
[http://dx.doi.org/10.1038/nm.2112] [PMID: 20228816]
[93]
Shen, K.; Luk, S.; Hicks, D.F.; Elman, J.S.; Bohr, S.; Iwamoto, Y.; Murray, R.; Pena, K.; Wang, F.; Seker, E.; Weissleder, R.; Yarmush, M.L.; Toner, M.; Sgroi, D.; Parekkadan, B. Resolving cancer-stroma interfacial signalling and interventions with micropatterned tumour-stromal assays. Nat. Commun., 2014, 5, 5662.
[http://dx.doi.org/10.1038/ncomms6662] [PMID: 25489927]
[94]
Ertel, A.; Verghese, A.; Byers, S.W.; Ochs, M.; Tozeren, A. Pathway-specific differences between tumor cell lines and normal and tumor tissue cells. Mol. Cancer, 2006, 5(1), 55.
[http://dx.doi.org/10.1186/1476-4598-5-55] [PMID: 17081305]
[95]
Stein, W.D.; Litman, T.; Fojo, T.; Bates, S.E. A Serial Analysis of Gene Expression (SAGE) database analysis of chemosensitivity: comparing solid tumors with cell lines and comparing solid tumors from different tissue origins. Cancer Res., 2004, 64(8), 2805-2816.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-3383] [PMID: 15087397]
[96]
Gillet, J.P.; Calcagno, A.M.; Varma, S.; Marino, M.; Green, L.J.; Vora, M.I.; Patel, C.; Orina, J.N.; Eliseeva, T.A.; Singal, V.; Padmanabhan, R.; Davidson, B.; Ganapathi, R.; Sood, A.K.; Rueda, B.R.; Ambudkar, S.V.; Gottesman, M.M. Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance. Proc. Natl. Acad. Sci. USA, 2011, 108(46), 18708-18713.
[http://dx.doi.org/10.1073/pnas.1111840108] [PMID: 22068913]
[97]
Yung, W.K.; Shapiro, J.R.; Shapiro, W.R. Heterogeneous chemosensitivities of subpopulations of human glioma cells in culture. Cancer Res., 1982, 42(3), 992-998.
[PMID: 7199383]
[98]
Iwadate, Y.; Mochizuki, S.; Fujimoto, S.; Namba, H.; Sakiyama, S.; Tagawa, M.; Yamaura, A. Alteration of CDKN2/p16 in human astrocytic tumors is related with increased susceptibility to antimetabolite anticancer agents. Int. J. Oncol., 2000, 17(3), 501-505.
[http://dx.doi.org/10.3892/ijo.17.3.501] [PMID: 10938390]
[99]
Jackson, S.E.; Chester, J.D. Personalised cancer medicine. Int. J. Cancer, 2015, 137(2), 262-266.
[http://dx.doi.org/10.1002/ijc.28940] [PMID: 24789362]
[100]
Jemaà, M.; Manic, G.; Lledo, G.; Lissa, D.; Reynes, C.; Morin, N.; Chibon, F.; Sistigu, A.; Castedo, M.; Vitale, I.; Kroemer, G.; Abrieu, A. Whole-genome duplication increases tumor cell sensitivity to MPS1 inhibition. Oncotarget, 2016, 7(1), 885-901.
[http://dx.doi.org/10.18632/oncotarget.6432] [PMID: 26637805]
[101]
Vleugel, M.; Hoogendoorn, E.; Snel, B.; Kops, G.J. Evolution and function of the mitotic checkpoint. Dev. Cell, 2012, 23(2), 239-250.
[http://dx.doi.org/10.1016/j.devcel.2012.06.013] [PMID: 22898774]
[102]
Liu, D.; Vader, G.; Vromans, M.J.; Lampson, M.A.; Lens, S.M. Sensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates. Science, 2009, 323(5919), 1350-1353.
[http://dx.doi.org/10.1126/science.1167000] [PMID: 19150808]
[103]
London, N.; Biggins, S. Mad1 kinetochore recruitment by Mps1-mediated phosphorylation of Bub1 signals the spindle checkpoint. Genes Dev., 2014, 28(2), 140-152.
[http://dx.doi.org/10.1101/gad.233700.113] [PMID: 24402315]
[104]
Ji, Z.; Gao, H.; Yu, H. CELL DIVISION CYCLE. Kinetochore attachment sensed by competitive Mps1 and microtubule binding to Ndc80C. Science, 2015, 348(6240), 1260-1264.
[http://dx.doi.org/10.1126/science.aaa4029] [PMID: 26068854]
[105]
Jemaà, M.; Galluzzi, L.; Kepp, O.; Boilève, A.; Lissa, D.; Senovilla, L.; Harper, F.; Pierron, G.; Berardinelli, F.; Antoccia, A.; Castedo, M.; Vitale, I.; Kroemer, G. Preferential killing of p53-deficient cancer cells by reversine. Cell Cycle, 2012, 11(11), 2149-2158.
[http://dx.doi.org/10.4161/cc.20621] [PMID: 22592527]

Rights & Permissions Print Cite
Article Metrics
25
1
1
© 2024 Bentham Science Publishers | Privacy Policy