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Anti-Cancer Agents in Medicinal Chemistry

Author(s): Saeedeh Rostampour, Farhad Eslami, Esmaeil Babaei, Hossein Mostafavi and Majid Mahdavi*

DOI: 10.2174/0118715206272359231121105713

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An Active Compound from the Pyrazine Family Induces Apoptosis by Targeting the Bax/Bcl2 and Survivin Expression in Chronic Myeloid Leukemia K562 Cells

Page: [203 - 212] Pages: 10

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Abstract

Background: It has been established that pyrazine derivatives, which have widespread bioactivities, can effectively treat cancer.

Objectives: In this study, we investigated the effects of 2-methoxy-5-(oxiran-2-ylmethyl) phenyl pyrazine-2- carboxylate (2-mOPP), a new pyrazine derivative, on proliferation, viability, and apoptosis induction in human leukemia K562 cells.

Methods: For this purpose, the K562 cells were treated with various concentrations (20-120 μM) of the 2-mOPP for 24-72 hours. Cell viability was determined by MTT growth inhibition assay. Apoptotic activity of 2-mOPP was investigated morphologically by Hoechst staining, cell surface expression assay of phosphatidylserine by Annexin-V/PI technique, as well as DNA fragmentation assay. The effect of 2-mOPP on the K562 cell cycle was studied by flow cytometry. To determine the impact of 2-mOPP on the expression of intrinsic apoptosis-related genes, Bcl2 (anti-apoptotic), Bax (pro-apoptotic), and Survivin genes expression levels were evaluated before and after treatment with 2-mOPP through Real-Time PCR analysis.

Results: The results revealed that 2-mOPP inhibited viability with IC50 of 25μM in 72 h. Morphological changes assessment by fluorescence microscopy, Annexin V/PI double staining by flow cytometry, and DNA ladders formation upon cell treatment with the 2-mOPP showed that this compound induces apoptosis at IC50 value. Cell cycle arrest was observed in the G0/G1 phase, and the sub-G1 cell population (the sign of apoptosis) increased in a time-dependent manner. Low expression levels of Bcl2 and Survivin in K562 cells were observed 24-72 h after treatment. Along with the down-regulation of Survivin and Bcl2, the expression of Bax was increased after treatment with 2-mOPP.

Conclusion: These findings demonstrate that the new pyrazine derivative plays a crucial role in blocking the proliferation of the leukemic cells by inducing cell cycle arrest and apoptosis.

Graphical Abstract

[1]
Schmitt, C.A. Senescence, apoptosis and therapy — cutting the lifelines of cancer. Nat. Rev. Cancer, 2003, 3(4), 286-295.
[http://dx.doi.org/10.1038/nrc1044] [PMID: 12671667]
[2]
Schulze-Bergkamen, H.; Krammer, P.H. Apoptosis in cancer—implications for therapy. Semin. Oncol., 2004, 31(1), 90-119.
[http://dx.doi.org/10.1053/j.seminoncol.2003.11.006] [PMID: 14970941]
[3]
Stefanis, L.; Burke, R.E.; Greene, L.A. Apoptosis in neurodegenerative disorders. Curr. Opin. Neurol., 1997, 10(4), 299-305.
[http://dx.doi.org/10.1097/00019052-199708000-00004] [PMID: 9266153]
[4]
Elmore, S. Apoptosis: A review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516.
[http://dx.doi.org/10.1080/01926230701320337] [PMID: 17562483]
[5]
Fridman, J.S.; Lowe, S.W. Control of apoptosis by p53. Oncogene, 2003, 22, 9030-9040.
[http://dx.doi.org/10.1038/sj.onc.1207116]
[6]
Yin, X.M. Signal transduction mediated by Bid, a pro-death Bcl-2 family proteins, connects the death receptor and mitochondria apoptosis pathways. Cell Res., 2000, 10(3), 161-167.
[http://dx.doi.org/10.1038/sj.cr.7290045] [PMID: 11032168]
[7]
Tzifi, F.; Economopoulou, C.; Gourgiotis, D.; Ardavanis, A.; Papageorgiou, S.; Scorilas, A. The role of BCL2 family of apoptosis regulator proteins in acute and chronic leukemias. Adv. Hematol., 2012, 2012, 524308.
[http://dx.doi.org/10.1155/2012/524308]
[8]
Sakamoto, S.; Kyprianou, N. Targeting anoikis resistance in prostate cancer metastasis. Mol. Aspects Med., 2010, 31(2), 205-214.
[http://dx.doi.org/10.1016/j.mam.2010.02.001] [PMID: 20153362]
[9]
Mahdavi, M.; Davoodi, J.; Zali, M.R.; Foroumadi, A. Concomitant activation of caspase-9 and down-regulation of IAP proteins as a mechanism of apoptotic death in HepG2, T47D and HCT-116 cells upon exposure to a derivative from 4-aryl-4H-chromenes family. Biomed. Pharmacother., 2011, 65(3), 175-182.
[http://dx.doi.org/10.1016/j.biopha.2011.03.001] [PMID: 21565459]
[10]
Deveraux, Q.L.; Stennicke, H.R.; Salvesen, G.S.; Reed, J.C. Endogenous inhibitors of caspases. J. Clin. Immunol., 1999, 19(6), 388-398.
[http://dx.doi.org/10.1023/A:1020502800208] [PMID: 10634212]
[11]
Clem, R.J.; Sheu, T.T.; Richter, B.M.; He, W.W.; Thornberry, N.A.; Duckett, C.S.; Hardwick, J.M. c-IAP1 is cleaved by caspases to produce a proapoptotic C-terminal fragment. J. Biol. Chem., 2001, 276(10), 7602-7608.
[http://dx.doi.org/10.1074/jbc.M010259200] [PMID: 11106668]
[12]
Nachmias, B.; Ashhab, Y.; Bucholtz, V.; Drize, O.; Kadouri, L.; Lotem, M.; Peretz, T.; Mandelboim, O.; Ben-Yehuda, D. Caspase-mediated cleavage converts Livin from an antiapoptotic to a proapoptotic factor: Implications for drug-resistant melanoma. Cancer Res., 2003, 63(19), 6340-6349.
[PMID: 14559822]
[13]
Lozzio, B.B.; Lozzio, C.B. Properties and usefulness of the original K-562 human myelogenous leukemia cell line. Leuk. Res., 1979, 3(6), 363-370.
[http://dx.doi.org/10.1016/0145-2126(79)90033-X] [PMID: 95026]
[14]
Chen, Y.; Peng, C.; Sullivan, C.; Li, D.; Li, S. Critical molecular pathways in cancer stem cells of chronic myeloid leukemia. Leukemia, 2010, 24(9), 1545-1554.
[http://dx.doi.org/10.1038/leu.2010.143] [PMID: 20574455]
[15]
Chang, G.; Zhang, H.; Wang, J.; Zhang, Y.; Xu, H.; Wang, C.; Zhang, H.; Ma, L.; Li, Q.; Pang, T. CD44 targets Wnt/β-catenin pathway to mediate the proliferation of K562 cells. Cancer Cell Int., 2013, 13(1), 117.
[http://dx.doi.org/10.1186/1475-2867-13-117] [PMID: 24257075]
[16]
Calabretta, B.; Perrotti, D. The biology of CML blast crisis. Blood, 2004, 103(11), 4010-4022.
[http://dx.doi.org/10.1182/blood-2003-12-4111] [PMID: 14982876]
[17]
Quintás-Cardama, A.; Cortes, J. Molecular biology of bcr-abl1–positive chronic myeloid leukemia. Blood, 2009, 113(8), 1619-1630.
[http://dx.doi.org/10.1182/blood-2008-03-144790] [PMID: 18827185]
[18]
Moosavi, M.A.; Yazdanparast, R.; Lotfi, A. ERK1/2 inactivation and p38 MAPK-dependent caspase activation during guanosine 5′-triphosphate-mediated terminal erythroid differentiation of K562 cells. Int. J. Biochem. Cell Biol., 2007, 39(9), 1685-1697.
[http://dx.doi.org/10.1016/j.biocel.2007.04.016] [PMID: 17543571]
[19]
de Lima, A.P.; de Castro, P.F.; Vilanova-Costa, C.A.S.T. Mariana dos, S.M.F.; de Santana, B.B.R.A.; Benfica, P.L.; Valadares, M.C.; Pavanin, L.A.; dos Santos, W.B.; de Paula, S.L.E. The compound cis-(dichloro)tetrammineruthenium(III) chloride induces caspase-mediated apoptosis in K562 cells. Toxicol. In Vitro, 2010, 24(6), 1562-1568.
[http://dx.doi.org/10.1016/j.tiv.2010.06.015] [PMID: 20600797]
[20]
Druker, B.J.; Guilhot, F.; O’Brien, S.G.; Gathmann, I.; Kantarjian, H.; Gattermann, N.; Deininger, M.W.N.; Silver, R.T.; Goldman, J.M.; Stone, R.M.; Cervantes, F.; Hochhaus, A.; Powell, B.L.; Gabrilove, J.L.; Rousselot, P.; Reiffers, J.; Cornelissen, J.J.; Hughes, T.; Agis, H.; Fischer, T.; Verhoef, G.; Shepherd, J.; Saglio, G.; Gratwohl, A.; Nielsen, J.L.; Radich, J.P.; Simonsson, B.; Taylor, K.; Baccarani, M.; So, C.; Letvak, L.; Larson, R.A. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N. Engl. J. Med., 2006, 355(23), 2408-2417.
[http://dx.doi.org/10.1056/NEJMoa062867] [PMID: 17151364]
[21]
Abdel-Aziz, H.A.; El-Zahabi, H.S.A.; Dawood, K.M. Microwave-assisted synthesis and in vitro anti-tumor activity of 1,3,4-triaryl-5-N-arylpyrazole-carboxamides. Eur. J. Med. Chem., 2010, 45(6), 2427-2432.
[http://dx.doi.org/10.1016/j.ejmech.2010.02.026] [PMID: 20207452]
[22]
Maga, J.A. Pyrazine update. Food Rev. Int., 1992, 8(4), 479-558.
[http://dx.doi.org/10.1080/87559129209540951]
[23]
Barlin, G.B. The Pyrazines: The Chemistry of Heterocyclic Compounds: A series of monographs; John Wiley & Sons: New York, 1982, 41, p. 1-10.
[24]
Adams, J.; Kauffman, M. Development of the proteasome inhibitor Velcade (Bortezomib). Cancer Invest., 2004, 22(2), 304-311.
[http://dx.doi.org/10.1081/CNV-120030218] [PMID: 15199612]
[25]
Barlin, G.B. The Pyrazines: The Chemistry of Heterocyclic Compounds: A series of monographs; John Wiley & Sons: New York, 1982, 41, p. 1-10.
[26]
Miniyar, P.; Murumkar, P.; Patil, P.; Barmade, M.; Bothara, K. Unequivocal role of pyrazine ring in medicinally important compounds: A review. Mini Rev. Med. Chem., 2013, 13(11), 1607-1625.
[http://dx.doi.org/10.2174/1389557511313110007] [PMID: 23544468]
[27]
Cynamon, M.H.; Gimi, R.; Gyenes, F.; Sharpe, C.A.; Bergmann, K.E.; Han, H.J.; Gregor, L.B.; Rapolu, R.; Luciano, G.; Welch, J.T. Pyrazinoic acid esters with broad spectrum in vitro antimycobacterial activity. J. Med. Chem., 1995, 38(20), 3902-3907.
[http://dx.doi.org/10.1021/jm00020a003] [PMID: 7562923]
[28]
Simões, M.F.; Valente, E.; Gómez, M.J.R.; Anes, E.; Constantino, L. Lipophilic pyrazinoic acid amide and ester prodrugs. Eur. J. Pharm. Sci., 2009, 37(3-4), 257-263.
[http://dx.doi.org/10.1016/j.ejps.2009.02.012] [PMID: 19491013]
[29]
Khani-Meinagh, H.; Mostafavi, H.; Reiling, N.; Mahdavi, M.; Zarrini, G. Design, synthesis and evaluation of biological activities of some novel anti-TB agents with bio-reducible functional group. Bioimpacts, 2019, 9(4), 199-209.
[http://dx.doi.org/10.15171/bi.2019.25] [PMID: 31799156]
[30]
Zhou, H.; Yu, Y.; Li, H.; Shi, W.; Yang, H.; Liu, C.; Wang, S.; Yu, M. Anti-H can trigger apoptosis and down-regulate FUT1 expression in erythroid differentiated K562 cells without complement mediation. Transpl. Immunol., 2012, 27(4), 151-156.
[http://dx.doi.org/10.1016/j.trim.2012.10.001] [PMID: 23063462]
[31]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[32]
Eslami, F.; Mahdavi, M.; Babaei, E.; Hussen, B.M.; Mostafavi, H.; Shahbazi, A.; Hidayat, H.J. Down-regulation of Survivin and Bcl-2 concomitant with the activation of caspase-3 as a mechanism of apoptotic death in KG1a and K562 cells upon exposure to a derivative from ciprofloxacin family. Toxicol. Appl. Pharmacol., 2020, 409(November), 115331.
[http://dx.doi.org/10.1016/j.taap.2020.115331] [PMID: 33171188]
[33]
Nicoletti, I.; Migliorati, G.; Pagliacci, M.C.; Grignani, F.; Riccardi, C. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J. Immunol. Methods, 1991, 139(2), 271-279.
[http://dx.doi.org/10.1016/0022-1759(91)90198-O] [PMID: 1710634]
[34]
Uchakina, O.N.; Ban, H.; McKallip, R.J. Targeting hyaluronic acid production for the treatment of leukemia: Treatment with 4-methylumbelliferone leads to induction of MAPK-mediated apoptosis in K562 leukemia. Leuk. Res., 2013, 37(10), 1294-1301.
[http://dx.doi.org/10.1016/j.leukres.2013.07.009] [PMID: 23876826]
[35]
Finaurini, S.; Basilico, N.; Corbett, Y.; D’Alessandro, S.; Parapini, S.; Olliaro, P.; Haynes, R.K.; Taramelli, D. Dihydroartemisinin inhibits the human erythroid cell differentiation by altering the cell cycle. Toxicology, 2012, 300(1-2), 57-66.
[http://dx.doi.org/10.1016/j.tox.2012.05.024] [PMID: 22677887]
[36]
Kalle, A.M.; Sachchidanand, S.; Pallu, R. Bcr–Abl-independent mechanism of resistance to imatinib in K562 cells: Induction of cyclooxygenase-2 (COX-2) by histone deacetylases (HDACs). Leuk. Res., 2010, 34(9), 1132-1138.
[http://dx.doi.org/10.1016/j.leukres.2010.01.030] [PMID: 20206383]
[37]
Zheng, L.W.; Shao, J.H.; Zhao, B.X.; Miao, J.Y. Synthesis of novel pyrazolo[1,5- a]pyrazin-4(5 H)-one derivatives and their inhibition against growth of A549 and H322 lung cancer cells. Bioorg. Med. Chem. Lett., 2011, 21(13), 3909-3913.
[http://dx.doi.org/10.1016/j.bmcl.2011.05.035] [PMID: 21640587]
[38]
Zhang, J.H.; Fan, C.D.; Zhao, B.X.; Shin, D.S.; Dong, W.L.; Xie, Y.S.; Miao, J.Y. Synthesis and preliminary biological evaluation of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as potential agents against A549 lung cancer cells. Bioorg. Med. Chem., 2008, 16(24), 10165-10171.
[http://dx.doi.org/10.1016/j.bmc.2008.10.066] [PMID: 19013820]
[39]
Ghodousi-Dehnavi, E.; Hosseini, R.H.; Arjmand, M.; Nasri, S.; Zamani, Z. A metabolomic investigation of eugenol on colorectal cancer cell line HT-29 by modifying the expression of APC, p53, and KRAS genes. eCAM, 2021, 2021, 1448206.
[40]
Sahdev, A.K.; Raj, V.; Singh, A.K.; Rai, A.; Keshari, A.K.; De, A.; Samanta, A.; Kumar, U.; Rawat, A.; Kumar, D.; Nath, S.; Prakash, A.; Saha, S. Ameliorative effects of pyrazinoic acid against oxidative and metabolic stress manifested in rats with dimethylhydrazine induced colonic carcinoma. Cancer Biol. Ther., 2017, 18(5), 304-313.
[http://dx.doi.org/10.1080/15384047.2017.1310341] [PMID: 28358223]
[41]
Crawford, L.J.A.; Walker, B.; Ovaa, H.; Chauhan, D.; Anderson, K.C.; Morris, T.C.M.; Irvine, A.E. Comparative selectivity and specificity of the proteasome inhibitors BzLLLCOCHO, PS-341, and MG-132. Cancer Res., 2006, 66(12), 6379-6386.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-0605] [PMID: 16778216]
[42]
Chauhan, D.; Hideshima, T.; Mitsiades, C.; Richardson, P.; Anderson, K.C. Proteasome inhibitor therapy in multiple myeloma. Mol. Cancer Ther., 2005, 4(4), 686-692.
[http://dx.doi.org/10.1158/1535-7163.MCT-04-0338] [PMID: 15827343]
[43]
Ri, M.; Iida, S.; Ishida, T.; Ito, A.; Yano, H.; Inagaki, A.; Ding, J.; Kusumoto, S.; Komatsu, H.; Utsunomiya, A.; Ueda, R. Bortezomib‐induced apoptosis in mature T‐cell lymphoma cells partially depends on upregulation of Noxa and functional repression of Mcl‐1. Cancer Sci., 2009, 100(2), 341-348.
[http://dx.doi.org/10.1111/j.1349-7006.2008.01038.x] [PMID: 19068089]
[44]
Hideshima, T.; Mitsiades, C.; Akiyama, M.; Hayashi, T.; Chauhan, D.; Richardson, P.; Schlossman, R.; Podar, K.; Munshi, N.C.; Mitsiades, N.; Anderson, K.C. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood, 2003, 101(4), 1530-1534.
[http://dx.doi.org/10.1182/blood-2002-08-2543] [PMID: 12393500]
[45]
Mitsiades, N.; Mitsiades, C.S.; Richardson, P.G.; Poulaki, V.; Tai, Y.T.; Chauhan, D.; Fanourakis, G.; Gu, X.; Bailey, C.; Joseph, M.; Libermann, T.A.; Schlossman, R.; Munshi, N.C.; Hideshima, T.; Anderson, K.C. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: Therapeutic applications. Blood, 2003, 101(6), 2377-2380.
[http://dx.doi.org/10.1182/blood-2002-06-1768] [PMID: 12424198]
[46]
Gartel, A.L.; Feliciano, C.; Tyner, A.L. A new method for determining the status of p53 in tumor cell lines of different origin. Oncol. Res., 2003, 13(6), 405-408.
[http://dx.doi.org/10.3727/096504003108748429] [PMID: 12725531]
[47]
Nylander, K.; Dabelsteen, E.; Hall, P.A. The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neck. J. Oral Pathol. Med., 2000, 29(9), 413-425.
[http://dx.doi.org/10.1034/j.1600-0714.2000.290901.x]
[48]
Oltval, Z.N.; Milliman, C.L.; Korsmeyer, S.J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death. Cell, 1993, 74(4), 609-619.
[http://dx.doi.org/10.1016/0092-8674(93)90509-O] [PMID: 8358790]
[49]
Hockenbery, D.; Nuñez, G.; Milliman, C.; Schreiber, R.D.; Korsmeyer, S.J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature, 1990, 348(6299), 334-336.
[http://dx.doi.org/10.1038/348334a0] [PMID: 2250705]
[50]
Krajewski, S.; Tanaka, S.; Takayama, S.; Schibler, M.J.; Fenton, W.; Reed, J.C. Investigation of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes. Cancer Res., 1993, 53(19), 4701-4714.
[PMID: 8402648]
[51]
de Jong, D.; Prins, F.A.; Mason, D.Y.; Reed, J.C.; van Ommen, G.B.; Kluin, P.M. Subcellular localization of the bcl-2 protein in malignant and normal lymphoid cells. Cancer Res., 1994, 54(1), 256-260.
[PMID: 8261449]
[52]
Zhu, W.; Cowie, A.; Wasfy, G.W.; Penn, L.Z.; Leber, B.; Andrews, D.W. Bcl-2 mutants with restricted subcellular location reveal spatially distinct pathways for apoptosis in different cell types. EMBO J., 1996, 15(16), 4130-4141.
[http://dx.doi.org/10.1002/j.1460-2075.1996.tb00788.x] [PMID: 8861942]
[53]
Hsu, Y.T.; Youle, R.J. Nonionic detergents induce dimerization among members of the Bcl-2 family. J. Biol. Chem., 1997, 272(21), 13829-13834.
[http://dx.doi.org/10.1074/jbc.272.21.13829] [PMID: 9153240]
[54]
Gross, A.; Jockel, J.; Wei, M.C.; Korsmeyer, S.J. Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis. EMBO J., 1998, 17(14), 3878-3885.
[http://dx.doi.org/10.1093/emboj/17.14.3878] [PMID: 9670005]
[55]
Puthalakath, H.; Huang, D.C.S.; O’Reilly, L.A.; King, S.M.; Strasser, A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol. Cell, 1999, 3(3), 287-296.
[http://dx.doi.org/10.1016/S1097-2765(00)80456-6] [PMID: 10198631]
[56]
Wolter, K.G.; Hsu, Y.T.; Smith, C.L.; Nechushtan, A.; Xi, X.G.; Youle, R.J. Movement of Bax from the cytosol to mitochondria during apoptosis. J. Cell Biol., 1997, 139(5), 1281-1292.
[http://dx.doi.org/10.1083/jcb.139.5.1281] [PMID: 9382873]
[57]
Teijido, O.; Dejean, L. Upregulation of Bcl2 inhibits apoptosis-driven BAX insertion but favors BAX relocalization in mitochondria. FEBS Lett., 2010, 584(15), 3305-3310.
[http://dx.doi.org/10.1016/j.febslet.2010.07.002] [PMID: 20621101]
[58]
Pavlović V.; Cekić S.; Kocić G.; Sokolović D.; Živković V. Effect of monosodium glutamate on apoptosis and Bcl-2/Bax protein level in rat thymocyte culture. Physiol. Res., 2007, 56(5), 619-626.
[http://dx.doi.org/10.33549/physiolres.931064] [PMID: 17184147]
[59]
Jiang, H.; Hou, C.; Zhang, S.; Xie, H.; Zhou, W.; Jin, Q.; Cheng, X.; Qian, R.; Zhang, X. Matrine upregulates the cell cycle protein E2F-1 and triggers apoptosis via the mitochondrial pathway in K562 cells. Eur. J. Pharmacol., 2007, 559(2-3), 98-108.
[http://dx.doi.org/10.1016/j.ejphar.2006.12.017] [PMID: 17291488]
[60]
Jia, H.Y.; Wu, J.X.; Zhu, X.F.; Chen, J.M.; Yang, S.P.; Yan, H.J.; Tan, L.; Zeng, Y.X.; Huang, W. ZD6474 inhibits Src kinase leading to apoptosis of imatinib-resistant K562 cells. Leuk. Res., 2009, 33(11), 1512-1519.
[http://dx.doi.org/10.1016/j.leukres.2009.03.033] [PMID: 19394692]
[61]
Takahashi, R.; Deveraux, Q.; Tamm, I.; Welsh, K.; Assa-Munt, N.; Salvesen, G.S.; Reed, J.C. A single BIR domain of XIAP sufficient for inhibiting caspases. J. Biol. Chem., 1998, 273(14), 7787-7790.
[http://dx.doi.org/10.1074/jbc.273.14.7787] [PMID: 9525868]
[62]
Li, F.; Ackermann, E.J.; Bennett, C.F.; Rothermel, A.L.; Plescia, J.; Tognin, S.; Villa, A.; Marchisio, P.C.; Altieri, D.C. Pleiotropic cell-division defects and apoptosis induced by interference with survivin function. Nat. Cell Biol., 1999, 1(8), 461-466.
[http://dx.doi.org/10.1038/70242] [PMID: 10587640]
[63]
Kawasaki, H.; Altieri, D.C.; Lu, C.D.; Toyoda, M.; Tenjo, T.; Tanigawa, N. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res., 1998, 58(22), 5071-5074.
[PMID: 9823313]
[64]
Kawasaki, H.; Toyoda, M.; Shinohara, H.; Okuda, J.; Watanabe, I.; Yamamoto, T.; Tanaka, K.; Tenjo, T.; Tanigawa, N. Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis. Cancer, 2001, 91(11), 2026-2032.
[http://dx.doi.org/10.1002/1097-0142(20010601)91:11<2026:AID-CNCR1228>3.0.CO;2-E] [PMID: 11391581]
[65]
Kato, J.; Kuwabara, Y.; Mitani, M.; Shinoda, N.; Sato, A.; Toyama, T.; Mitsui, A.; Nishiwaki, T.; Moriyama, S.; Kudo, J.; Fujii, Y. Expression of survivin in esophageal cancer: Correlation with the prognosis and response to chemotherapy. Int. J. Cancer, 2001, 95(2), 92-95.
[http://dx.doi.org/10.1002/1097-0215(20010320)95:2<92:AID-IJC1016>3.0.CO;2-9] [PMID: 11241318]
[66]
Ikeguchi, M.; Yamaguchi, K.; Kaibara, N. Survivin gene expression positively correlates with proliferative activity of cancer cells in esophageal cancer. Tumour Biol., 2003, 24(1), 40-45.
[http://dx.doi.org/10.1159/000070659] [PMID: 12743425]
[67]
Ikeguchi, M.; Kaibara, N. survivin messenger RNA expression is a good prognostic biomarker for oesophageal carcinoma. Br. J. Cancer, 2002, 87(8), 883-887.
[http://dx.doi.org/10.1038/sj.bjc.6600546] [PMID: 12373603]
[68]
Grabowski, P.; Kühnel, T.; Mühr-Wilkenshoff, F.; Heine, B.; Stein, H.; Höpfner, M.; Germer, C.T.; Scherübl, H. Prognostic value of nuclear survivin expression in oesophageal squamous cell carcinoma. Br. J. Cancer, 2003, 88(1), 115-119.
[http://dx.doi.org/10.1038/sj.bjc.6600696] [PMID: 12556969]
[69]
Kappler, M.; Köhler, T.; Kampf, C.; Diestelkötter, P.; Würl, P.; Schmitz, M.; Bartel, F.; Lautenschläger, C.; Rieber, E.P.; Schmidt, H.; Bache, M.; Taubert, H.; Meye, A. Increased survivin transcript levels: An independent negative predictor of survival in soft tissue sarcoma patients. Int. J. Cancer, 2001, 95(6), 360-363.
[PMID: 11668517]
[70]
Würl, P.; Kappler, M.; Meye, A.; Bartel, F.; Köhler, T.; Lautenschläger, C.; Bache, M.; Schmidt, H.; Taubert, H. Co-expression of survivin and TERT and risk of tumour-related death in patients with soft-tissue sarcoma. Lancet, 2002, 359(9310), 943-945.
[http://dx.doi.org/10.1016/S0140-6736(02)07990-4] [PMID: 11918915]
[71]
Chakravarti, A.; Noll, E.; Black, P.M.; Finkelstein, D.F.; Finkelstein, D.M.; Dyson, N.J.; Loeffler, J.S. Quantitatively determined survivin expression levels are of prognostic value in human gliomas. J. Clin. Oncol., 2002, 20(4), 1063-1068.
[http://dx.doi.org/10.1200/JCO.2002.20.4.1063] [PMID: 11844831]
[72]
Kleinschmidt-DeMasters, B.K.; Heinz, D.; McCarthy, P.J.; Bobak, J.B.; Lillehei, K.O.; Shroyer, A.L.W.; Shroyer, K.R. Survivin in Glioblastomas. Arch. Pathol. Lab. Med., 2003, 127(7), 826-833.
[http://dx.doi.org/10.5858/2003-127-826-SIG] [PMID: 12823036]
[73]
Lu, C.D.; Altieri, D.C.; Tanigawa, N. Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res., 1998, 58(9), 1808-1812.
[PMID: 9581817]
[74]
Satoh, K.; Kaneko, K.; Hirota, M.; Masamune, A.; Satoh, A.; Shimosegawa, T. Expression of survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors. Cancer, 2001, 92(2), 271-278.
[http://dx.doi.org/10.1002/1097-0142(20010715)92:2<271:AID-CNCR1319>3.0.CO;2-0] [PMID: 11466679]
[75]
Ikeguchi, M.; Ueda, T.; Sakatani, T.; Hirooka, Y.; Kaibara, N. Expression of survivin messenger RNA correlates with poor prognosis in patients with hepatocellular carcinoma. Diagn. Mol. Pathol., 2002, 11(1), 33-40.
[http://dx.doi.org/10.1097/00019606-200203000-00007] [PMID: 11854600]
[76]
Saitoh, Y.; Yaginuma, Y.; Ishikawa, M. Analysis of Bcl-2, bax and survivin genes in uterine cancer. Int. J. Oncol., 1999, 15(1), 137-141.
[http://dx.doi.org/10.3892/ijo.15.1.137] [PMID: 10375606]