Bcl-2 Family Proteins in Development and Treatment of Malignant Diseases

Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death. N Engl J Med 2009; 361(16): 1570-83.10.1056/NEJMra0901217376041919828534Search in Google Scholar

Jin Z, El-Deiry WS. Overview of cell death signalling pathways. Cancer Biol Ther 2005; 4(2): 139-163.10.4161/cbt.4.2.150815725726Search in Google Scholar

Degterev A, Boyce M, Yuan J. A decade of caspases. Oncogene 2003; 22(53): 8543-67.10.1038/sj.onc.120710714634618Search in Google Scholar

Youle RJ, Strasser A. The BCL-2 family proteins: opposite activities that mediate cell death. Nat. Rev. Mol. Cell Biol 2008; 9(1): 47-59.Search in Google Scholar

Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the bcl-2 gene in human follicular lymphoma. Science 1985; 228(4706): 1440-3.10.1126/science.38744303874430Search in Google Scholar

Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, Adams JM, Huang DC. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev 2005; 19(11): 1294-305.10.1101/gad.1304105114255315901672Search in Google Scholar

Willis SN, Fletcher JI, Kaufmann T, van Delft MF, Chen L, Czabotar PE, Ierino H, Lee EF, Fairlie WD, Bouillet P, Strasser A, Kluck RM, Adams JM, Huang DC. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 2007; 315(5813): 856-9.10.1126/science.113328917289999Search in Google Scholar

Kim H, Rafiuddin-Shah M, Tu HC, Jeffers JR, Zambetti GP, Hsieh J, Cheng E. Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies. Nat Cell Biol 2006; 8(12): 1348-58.10.1038/ncb149917115033Search in Google Scholar

Sax JK, El Deiry WS. p53 downstream targets and chemosensitivity. Cell Death Differ 2003; 10(4): 413-17.10.1038/sj.cdd.440122712719718Search in Google Scholar

Wu Y, Mehew JW, Heckman CA, Arcinas M, Boxer LM. Negative regulation of bcl-2 expression by p53 in hematopoietic cells. Oncogene 2001; 20(2): 240-51.10.1038/sj.onc.120406711313951Search in Google Scholar

Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Schuler M, Green DR. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 2004; 303(60): 1010-4.10.1126/science.109273414963330Search in Google Scholar

Cotter TG. Apoptosis and cancer: the genesis of a research field. Nat Rev Cancer. 2009; 9(7): 501-7.10.1038/nrc2663Search in Google Scholar

Wilson TR, Johnston PG, Longley DB. Anti-apoptotic mechanisms of drug resistance in cancer. Curr Cancer Drug Targets. 2009; 9(3): 307-19.10.2174/156800909788166547Search in Google Scholar

Amundson SA, Myers TG, Scudiero D, Kitada S, Reed JC, Fornace AJ. An informatics approach identifying markers of chemosensitivity in human cancer cell lines. Cancer Res 2000; 60(21): 6101-10.Search in Google Scholar

Hockenbery DM. Targeting mitochondria for cancer therapy. Environ Mol Mutagen. 2010; 51(5): 476-89.10.1002/em.20552Search in Google Scholar

Weiss LM, Warnke RA, Sklar J, Cleary ML. Molecular analysis of the t(14;18) chromosomal translocation in malignant lymphomas. N Engl J Med. 1987; 317(19): 1185-1189.10.1056/NEJM198711053171904Search in Google Scholar

Cleary ML, Smith SD, Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell 1986; 47(1): 19-28.10.1016/0092-8674(86)90362-4Search in Google Scholar

Bertheas MF, Bachy M, Magaud JP, Rimokh R, Vasselon C, Berger F, Oriol PC, Jaubert J, Reynaud J, Brizard CP, et al. t(2;18) and t(18;22) variant chromosomal translocations in B cell malignancies. Leuk Lymphoma. 1992; 8(3): 197-200.10.3109/104281992090549051490147Search in Google Scholar

Adachi M, Tefferi A, Greipp PR, Kipps TJ, Tsujimoto Y. Preferential linkage of bcl-2 to immunoglobulin light chain gene in chronic lymphocytic leukemia. J Exp Med 1990; 171(2): 559-64.10.1084/jem.171.2.55921877272106002Search in Google Scholar

Hanada M, Delia D, Aiello A, Stadtmauer E, Reed JC. bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood. 1993; 82(6): 1820-1828.10.1182/blood.V82.6.1820.1820Search in Google Scholar

Monni O, Joensuu H, Franssila K, Klefstrom J, Alitalo K, Knuutila S. BCL2 overexpression associated with chromosomal amplification in diffuse large B-cell lymphoma. Blood. 1997; 90(3): 1168-1174.10.1182/blood.V90.3.1168Search in Google Scholar

Thomadaki H, Scorilas A. BCL2 family of apoptosis-related genes: functions and clinical implications in cancer. Crit Rev Clin Lab Sci 2006; 43(1): 1-67.10.1080/1040836050029562616531274Search in Google Scholar

Tothova E, Fricova M, Stecova N, Kafkova A, Elbertova A. High expression of Bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy. Neoplasma 2002; 49(3): 141-44.Search in Google Scholar

Castle VP, Heidelberger KP, Bromberg J, Ou X, Dole M, Nuñez G. Expression of the apoptosis-suppressing protein bcl-2, in neuroblastoma is associated with unfavourable histology and N-myc amplification. Am J Pathol 1993; 143(6): 1543-50.Search in Google Scholar

Jiang SX, Sato Y, Kuwao S, Kameya T. Expression of bcl-2 oncogene protein is prevalent in small cell lung carcinomas. J Pathol 1995; 177(2): 135-8.10.1002/path.1711770206Search in Google Scholar

Molica S, Mannella A, Dattilo A, Levato D, Iuliano F, Peta A, Consarino C, Magro S. Differential expression of BCL-2 oncoprotein and Fas antigen on normal peripheral blood and leukemic bone marrow cells. A flow cytometric analysis. Haematologica 1996; 81(4): 302-9.Search in Google Scholar

Klobusická M, Kusenda J, Babusíkova O. Expression of p53 and bcl-2 proteins in acute leukemias: an immunocytochemical study. Neoplasma 2001; 48(6): 489-95.Search in Google Scholar

Doglioni C, Dei Tos AP, Laurino L, Chiarelli C, Barbareschi M, Viale G. The prevalence of BCL-2 immunoreactivity in breast carcinomas and its clinicopathological correlates, with particular reference to oestrogen receptor status. Virchows Arch 1994; 424(1): 47-51.10.1007/BF00197392Search in Google Scholar

Krajewska M, Krajewski S, Epstein JI, Shabaik A, Sauvageot J, Song K, Kitada S, Reed JC. Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. Am J Pathol 1996; 148(5): 1567-76.Search in Google Scholar

Singhal S, Amin KM, Kruklitis R, Marshall MB, Kucharczuk JC, DeLong P, Litzky LA, Kaiser LR, Albelda SM. Differentially expressed apoptotic genes in early stage lung adenocarcinoma predicted by expression profiling. Cancer Biol Ther 2003; 2(5): 566-71.10.4161/cbt.2.5.514Search in Google Scholar

Watanabe J, Kushihata F, Honda K, Mominoki K, Matsuda S, Kobayashi N. BclxL overexpression in human hepatocellular carcinoma. Int J Oncol 2002; 21(3): 515-9.Search in Google Scholar

Krajewski S, Krajewska M, Ehrmann J, Sikorska M, Lach B, Chatten J, Reed JC. Immunohistochemical analysis of Bcl-2, Bcl-X, Mcl-1, and Bax in tumors of central and peripheral nervous system origin. Am J Pathol 1997; 150(3): 805-14.Search in Google Scholar

Krajewska M, Moss SF, Krajewski S, Song K, Holt PR, Reed JC. Elevated expression of Bcl-X and reduced Bak in primary colorectal adenocarcinomas. Cancer Res 1996; 56(10): 2422-7.Search in Google Scholar

Račay P, Hatok J, Hudeček J, Chudej J, Jurečeková J, Dobrota D. Transcription of genes of p53-dependent apoptosis in acute leukaemia. Int J Mol Med 2008; 22(6): 833-9.Search in Google Scholar

Gobé G, Rubin M, Williams G, Sawczuk I, Buttyan R. Apoptosis and expression of Bcl-2, Bcl-XL, and Bax in renal cell carcinomas. Cancer Invest 2002; 20(3): 324-32.10.1081/CNV-120001177Search in Google Scholar

Cho-Vega JH, Rassidakis GZ, Admirand JH, Oyarzo M, Ramalingam P, Paraguya A, McDonnell TJ, Amin HM, Medeiros LJ. MCL-1 expression in B-cell non-Hodgkin's lymphomas. Hum Pathol 2004; 35(9): 1095-100.10.1016/j.humpath.2004.04.018Search in Google Scholar

Rassidakis GZ, Lai R, McDonnell TJ, Cabanillas F, Sarris AH, Medeiros LJ. Overexpression of Mcl-1 in anaplastic large cell lymphoma cell lines and tumors. Am J Pathol 2002; 160(6): 2309-10.10.1016/S0002-9440(10)61178-9Search in Google Scholar

Wuillème-Toumi S, Robillard N, Gomez P, Moreau P, Le Gouill S, Avet-Loiseau H, Harousseau JL, Amiot M, Bataille R. Mcl-1 is overexpressed in multiple myeloma and associated with relapse and shorter survival. Leukemia 2005; 19(7): 1248-52.10.1038/sj.leu.240378415902294Search in Google Scholar

Wong RP, Khosravi S, Martinka M, Li G. Myeloid leukemia-1 expression in benign and malignant melanocytic lesions. Oncol Rep 2008; 19(4): 933-7.10.3892/or.19.4.933Search in Google Scholar

Lee HW, Lee SS, Lee SJ, Um HD. Bcl-w is expressed in a majority of infiltrative gastric adenocarcinomas and suppresses the cancer cell death by blocking stress-activated protein kinase/c-Jun NH2-terminal kinase activation. Cancer Res 2003; 63(5): 1093-100.Search in Google Scholar

Wilson JW, Nostro MC, Balzi M, Faraoni P, Cianchi F, Becciolini A, Potten CS. Bcl-w expression in colorectal adenocarcinoma. Br J Cancer 2000; 82(1): 178-85.10.1054/bjoc.1999.0897236318510638987Search in Google Scholar

MacCarthy-Morrogh L, Wood L, Brimmell M, Johnson PW, Packham G. Identification of a novel human BCLX promoter and exon. Oncogene 2000; 19(48): 5534-8.10.1038/sj.onc.120394911114731Search in Google Scholar

Yamaguchi H, Inokuchi K and Dan K: The study for loss of bcl-xs expression as a prognostic factor in acute myeloid leukemia. Leuk Res 2002; 26(12): 1119-23.10.1016/S0145-2126(02)00061-9Search in Google Scholar

Soussi T. p53 alterations in human cancers: more questions than answers. Oncogene 2007; 26(15): 2145-56.10.1038/sj.onc.1210280Search in Google Scholar

Inoue K, Kohno T, Takakura S, Hayashi Y, Mizoguchi H, Yokota J. Frequent microsatellite instability and BAX mutations in T cell acute lymphoblastic leukemia cell lines. Leuk Res 2000; 24(3): 255-62.10.1016/S0145-2126(99)00182-4Search in Google Scholar

Marone M, Ferrandina G, Macchia G, Mozzetti S, de Pasqua A, Benedetti-Panici P, Mancuso S, Scambia G. Bcl-2, Bax, Bcl-x(L) and Bcl-x(S) expression in neoplastic and normal endometrium. Oncology 2000; 58(2): 161-8.10.1159/00001209410705244Search in Google Scholar

Gil J, Yamamoto H, Zapata JM, Reed JC, Perucho M. Impairment of the proapoptotic activity of Bax by missense mutations found in gastrointestinal cancers. Cancer Res 1999; 59(9): 2034-7.Search in Google Scholar

Rampino, N., Yamamoto, H., Ionov, Y., Li, Y., Sawai, H., Reed, J. C., Perucho, M. Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science 1997; 275(5302): 967-9.10.1126/science.275.5302.9679020077Search in Google Scholar

Krajewska M, Fenoglio-Preiser CM, Krajewski S, Song K, Macdonald JS, Stemmerman G, Reed JC. Immunohistochemical analysis of Bcl-2 family proteins in adenocarcinomas of the stomach. Am J Pathol 1996; 149(5): 1449-57.Search in Google Scholar

Kondo S, Shinomura Y, Miyazaki Y, Kiyohara T, Tsutsui S, Kitamura S, Nagasawa Y, Nakahara M, Kanayama S, Matsuzawa Y. Mutations of the bak gene in human gastric and colorectal cancers. Cancer Res 2000; 60(16): 4328-30.Search in Google Scholar

Wani KM, Huilgol NG, Hongyo T, Shah K, Chatterjee N, Nair CK, Nomura T. Genetic alterations in the coding region of the bak gene in uterine cervical carcinoma. Br J Cancer 2003; 88(10): 1584-6.10.1038/sj.bjc.6600944237711112771926Search in Google Scholar

Kang MH, Reynolds P. Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res 2009; 15(4): 1126-32.10.1158/1078-0432.CCR-08-0144318226819228717Search in Google Scholar

Choi YH. Apoptosis of U937 human leukemic cells by sodium butyrate is associated with inhibition of telomerase activity. Int J Oncol 2006; 29(5): 1207-13.10.3892/ijo.29.5.1207Search in Google Scholar

Kelly TK, De Carvalho DD, Jones PA. Epigenetic modifications as therapeutic targets. Nat Biotechnol. 2010; 28(10): 1069-78.10.1038/nbt.1678302297220944599Search in Google Scholar

Kuendgen A, Gattermann N. Valproic acid for the treatment of myeloid malignancies. Cancer 2007; 110(5): 943-54.10.1002/cncr.2289117647267Search in Google Scholar

Klasa RJ, Gillum AM, Klem RE, Frankel SR. Oblimersen Bcl-2 antisense: Facilitating apoptosis in cancer treatment. Antisense Nucleic Acid Drug Dev 2002; 12(3): 193-213.10.1089/10872900276022079812162702Search in Google Scholar

O'Brien SM, Claxton DF, Crump M, Faderl S, Kipps T, Keating MJ, Viallet J, Cheson BD. Phase I study of obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist, in patients with advanced chronic chronic lymphocytic leukemia. Blood 2009; 113(2): 299-305.10.1182/blood-2008-02-137943496837218931344Search in Google Scholar

Di Cresce C, Koropatnick J. Antisense treatment in human prostate cancer and melanoma. Curr Cancer Drug Targets. 2010; 10(6): 555-65.10.2174/15680091079185945220482488Search in Google Scholar

Dalafave DS, Prisco G Inhibition of antiapoptotic BCL-XL, BCL-2 and MCL-1 proteins by small molecule mimetics. Cancer Inform. 2010; 9: 169-77.10.4137/CIN.S5065293582020838611Search in Google Scholar

Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer J, Kunzer AR, Letai A, Li Ch, Mitten MJ, Nettesheim DG, Ng S, Nimmer PM, O'Connor JM, Oleksijew A, Petros AM, Reed JC, Shen W, Tahir SK, Thompson CB, Tomaselli KJ, Wang B, Wendt MD, Zhang H, Fesik SW, Rosenberg SH. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005; 435(7042): 677-81.10.1038/nature0357915902208Search in Google Scholar

Vogler M, Dinsdale D, Sun XM, Young KW, Butterworth M, Nicotera P, Dyer MJS, Cohen GM A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells. Cell Death Differ 2008; 15(5), 820-30.10.1038/cdd.2008.2518309326Search in Google Scholar

Tse Ch, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S, Johnson F, Marsh K C, Mitten MJ, Nimmer P, Roberts L, Tahir SK, Xiao Y, Yang X, Zhang H, Fesik S, Rosenberg SH, Elmore SW ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 2008; 68(9): 3421-8.10.1158/0008-5472.CAN-07-583618451170Search in Google Scholar

Gandhi L, Camidge DR, Ribeiro de Oliveira M, Bonomi P, Gandara D, Khaira D, Hann CL, McKeegan EM, Litvinovich E, Hemken PM, Dive C, Enschede SH, Nolan C, Chiu YL, Busman T, Xiong H, Krivoshik AP, Humerickhouse R, Shapiro GI, Rudin CM. Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncol 2011; 29(7): 909-16.10.1200/JCO.2010.31.6208466828221282543Search in Google Scholar

Kögel D, Fulda S, Mittelbronn M. Therapeutic exploitation of apoptosis and autophagy for glioblastoma. Anticancer Agents Med Chem 2010; 10(6): 438-49.10.2174/187152061100906043820879985Search in Google Scholar

Nguyen M, Marcellus RC, Roulston A, Watson M, Serfass L, Murthy Madiraju SR, Goulet D, Viallet J, Bélec L, Billot X, Acoca S, Purisima E, Wiegmans A, Cluse L, Johnstone RW, Beauparlant P, Shore GC. Small molecule obatoclax (GX 15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc Natl Acad Sci USA 2007; 104(49), 19512-7.10.1073/pnas.0709443104214832018040043Search in Google Scholar

Schimmer AD, O'Brien S, Kantarjian H, Brandwein J, Cheson BD, Minden MD, Yee K, Ravandi F, Giles F, Schuh A, Gupta V, Andreeff M, Koller C., Chang H, Kamel-Reid S, Berger M, Viallet J, Borthakur G. A phase I study of the pan Bcl-2 family inhibitor obatoclax mesylate in patients with advances hematologic malignancies. Clin Cancer Res 2008; 14(24), 8295-301.10.1158/1078-0432.CCR-08-099919088047Search in Google Scholar

Hwang JJ, Kuruvilla J, Mendelson D, Pishvaian MJ, Deeken JF, Siu LL, Berger MS, Viallet J, Marshall JL. Phase I dose finding studies of obatoclax (GX15-070), a small molecule pan-BCL-2 family antagonist, in patients with advanced solid tumors or lymphoma. Clin Cancer Res 2010; 16(15): 4038-45.10.1158/1078-0432.CCR-10-0822370324520538761Search in Google Scholar

Konopleva M, Watt J, Contractor R, Tsao T, Harris D, Estrov Z, Bornmann W, Kantarjian H, Viallet J, Samudio I, Andreeff M. Mechanisms of antileukemic activity of the novel Bcl-2 homology domain-3 mimetic GX15-070 (obatoclax). Cancer Res 2008; 68(9): 3413-20.10.1158/0008-5472.CAN-07-1919409612718451169Search in Google Scholar

Paik PK, Rudin CM, Brown A, Rizvi NA, Takebe N, Travis W, James L, Ginsberg MS, Juergens R, Markus S, Tyson L, Subzwari S, Kris MG, Krug LM. A phase I study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in solid tumor malignancies. Cancer Chemother Pharmacol. 2010; 66(6): 1079-85.10.1007/s00280-010-1265-5294562520165849Search in Google Scholar

Oliver CL, Bauer JA, Wolker KG, Ubell ML, Narayan A. In vitro effect of the BH3 mimetic, (-)-gossypol, on head and neck squamous cell carcinoma cells. Clin Cancer Res 2004; 10(22): 7757-63.10.1158/1078-0432.CCR-04-055115570010Search in Google Scholar

Liu G, Kelly WK, Wilding G, Leopold L, Brill K, Somer B. An open-label, multicenter, phase I/II study of single-agent AT-101 in men with castrate-resistant prostate cancer. Clin Cancer Res 2009; 15(9): 3172-6.10.1158/1078-0432.CCR-08-2985292191519366825Search in Google Scholar

Heist RS, Fain J, Chinnasami B, Khan W, Molina JR, Sequist LV, Temel JS, Fidias P, Brainerd V, Leopold L, Lynch TJ. Phase I/II study of AT-101 with topotecan in relapsed and refractory small cell lung cancer. J Thorac Oncol 2010; 5(10): 1637-43.10.1097/JTO.0b013e3181e8f4dc20808253Search in Google Scholar