Withaferin A, a natural compound with anti-tumor activity, is a potent inhibitor of transcription factor C/EBPβ

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1864, Issue 7, 2017, Pages 1349-1358

  Falkenberg, Kim D ^a   Jakobs, Anke ^a   Matern, Julian C ^a   Dörner, Wolfgang ^a   Uttarkar, Sagar ^a   Trentmann, Amke ^a   Steinmann, Simone ^a   Coulibaly, Anna ^a   Schomburg, Caroline ^a   Mootz, Henning D ^a   Schmidt, Thomas J ^a   Klempnauer, Karl Heinz ^a  

^a UNIVERSITY OF MÜNSTER   (Germany)

Author keywords

C EBP ; Inhibitor; Myb; p300; Withaferin A

Indexed keywords

ANTINEOPLASTIC AGENT; CCAAT ENHANCER BINDING PROTEIN BETA; TRANSCRIPTION FACTOR; WITHAFERIN A; HISTONE ACETYLTRANSFERASE PCAF; PROTEIN BINDING; WITHANOLIDE;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BONE MARROW CELL; DRUG MECHANISM; GENE ACTIVATION; HL-60 CELL LINE; HUMAN; HUMAN CELL; NONHUMAN; PRIORITY JOURNAL; 3T3 CELL LINE; ANIMAL; ANTAGONISTS AND INHIBITORS; BINDING SITE; CHEMISTRY; METABOLISM; MOUSE; TUMOR CELL LINE;

3T3 CELLS; ANIMALS; ANTINEOPLASTIC AGENTS; BINDING SITES; CCAAT-ENHANCER-BINDING PROTEIN-BETA; CELL LINE, TUMOR; HUMANS; MICE; P300-CBP TRANSCRIPTION FACTORS; PROTEIN BINDING; WITHANOLIDES;

EID: 85019162790     PISSN: 01674889     EISSN: 18792596     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2017.05.003     Document Type: Article

References (54)

1. Ramsay, R.J., Gonda, T.J., Myb function in normal and cancer cells. Nat. Rev. Cancer 8 (2008), 523–534.
2. Clappier, E., Cuccuini, W., Kalota, A., Crinquette, A., Cayuela, J.M., Dik, W.A., Langerak, A.W., Montpellier, B., Nadel, B., Walrafen, P., Delattre, O., Aurias, A., Leblanc, T., Dombret, H., Gewirtz, A.M., Baruchel, A., Sigaux, F., Soulier, J., The C-MYB locus is involved in chromosomal translocation and genomic duplications in human T-cell acute leukemia (T-ALL), the translocation defining a new T-ALL subtype in very young children. Blood 110 (2007), 1251–1261.
3. Lahortiga, I., De Keersmaecker, K., Van Vlierberghe, P., Graux, C., Cauwelier, B., Lambert, F., Mentens, N., Beverloo, H.B., Pieters, R., Speleman, F., Odero, M.D., Bauters, M., Froyen, G., Marynen, P., Vandenberghe, P., Wlodarska, I., Meijerink, J.P., Cools, J., Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia. Nat. Genet. 39 (2007), 593–595.
4. Mansour, M.R., Abraham, B.J., Anders, L., Berezovskaya, A., Gutierrez, A., Durbin, A.D., Etchin, J., Lawton, L., Sallan, S.E., Silverman, L.B., Loh, M.L., Hunger, S.P., Sanda, T., Young, R.A., Look, A.T., Oncogene regulation. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science 346 (2014), 1373–1377.
5. Somervaille, T.C., Matheny, C.J., Spencer, G.J., Iwasaki, M., Rinn, J.L., Witten, D.M., Chang, H.Y., Shurtleff, S.A., Downing, J.R., Cleary, M.L., Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells. Cell Stem Cell 4 (2009), 129–140.
6. Zuber, J., Rappaport, A.R., Luo, W., Wang, E., Chen, C., Vaseva, A.V., Shi, J., Weissmueller, S., Fellmann, C., Taylor, M.J., Weissenboeck, M., Graeber, T.G., Kogan, S.C., Vakoc, C.R., Lowe, S.W., An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance. Genes Dev. 25 (2011), 1628–1640.
7. Persson, M., Andrén, Y., Mark, J., Horlings, H.M., Persson, F., Stenman, G., Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck. Proc. Natl. Acad. Sci. U. S. A. 106 (2009), 18740–18744.
8. Zhang, J., Wu, G., Miller, C.P., Tatevossian, R.G., Dalton, J.D., Tang, B., Orisme, W., Punchihewa, C., Parker, M., Qaddoumi, I., Boop, F.A., Lu, C., Kandoth, C., Ding, L., Lee, R., Huether, R., Chen, X., Hedlund, E., Nagahawatte, P., Rusch, M., Boggs, K., Cheng, J., Becksfort, J., Ma, J., Song, G., Li, Y., Wei, L., Wang, J., Shurtleff, S., Easton, J., Zhao, D., Fulton, R.S., Fulton, L.L., Dooling, D.J., Vadodaria, B., Mulder, H.L., Tang, C., Ochoa, K., Mullighan, C.G., Gajjar, A., Kriwacki, R., Sheer, D., Gilbertson, R.J., Mardis, E.R., Wilson, R.K., Downing, J.R., Baker, S.J., Ellison, D.W., St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project, Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat. Genet. 45 (2013), 602–612.
9. Pattabiraman, D.R., Gonda, T.J., Role and potential for therapeutic targeting of MYB in leukemia. Leukemia 27 (2013), 269–277.
10. Liu, X., Gold, K.A., Dmitrovsky, E., The Myb-p300 interaction is a novel molecular pharmacologic target. Mol. Cancer Ther. 14 (2015), 1273–1275.
11. Nerlov, C., The C/EBP family of transcription factors: a paradigm for interaction between gene expression and proliferation control. Trends Cell Biol. 17 (2007), 318–324.
12. Descombes, P., Schibler, U., A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA. Cell 67 (1991), 569–579.
13. Ossipow, V., Descombes, P., Schibler, U., CCAAT/enhancer-binding protein mRNA is translated into multiple proteins with different transcription activation potentials. Proc. Natl. Acad. Sci. U. S. A. 90 (1993), 8219–8223.
14. Calkhoven, C.F., Müller, C., Leutz, A., Translational control of C/EBPα and C/EBPβ isoform expression. Genes Dev. 14 (2000), 1920–1932.
15. Burk, O., Mink, S., Ringwald, M., Klempnauer, K.-H., Synergistic activation of the chicken mim-1 gene by v-myb and C/EBP transcription factors. EMBO J. 12 (1993), 2027–2038.
16. Ness, S.A., Kowentz-Leutz, E., Casini, T., Graf, T., Leutz, A., Myb and NF-M: combinatorial activators of myeloid genes in heterologous cell types. Genes Dev. 7 (1993), 749–759.
17. Roe, J.-S., Mercan, F., Rivera, K., Pappin, D.J., Vakoc, C.R., BET bromodomain inhibition suppresses the function of hematopoietic transcription factors in acute myeloid leukemia. Mol. Cell 58 (2015), 1028–1039.
18. Bujnicki, T., Wilczek, C., Schomburg, C., Feldmann, F., Schlenke, P., Müller-Tidow, C., Schmidt, T.J., Klempnauer, K.-H., Inhibition of Myb-dependent gene expression by the sesquiterpene lactone mexicanin-I. Leukemia 26 (2012), 615–622.
19. Schomburg, C., Naturstoffe als Inhibitoren c-Myb abhängiger Transkriptions-prozesse. Dissertation, 2013, Universität Münster.
20. Uttarkar, S., Dukare, S., Bopp, B., Goblirsch, M., Jose, J., Klempnauer, K.-H., Naphthol AS-E phosphate inhibits the activity of the transcription factor Myb by blocking the interaction with the KIX domain of the coactivator p300. Mol. Cancer Ther. 14 (2015), 1276–1285.
21. Uttarkar, S., Dasse, E., Coulibaly, A., Steinmann, S., Jakobs, A., Schomburg, C., Trentmann, A., Jose, J., Schlenke, P., Berdel, W.E., Schmidt, T.J., Müller-Tidow, C., Frampton, J., Klempnauer, K.-H., Targeting acute myeloid leukemia with a small molecule inhibitor of the Myb/p300 interaction. Blood 127 (2016), 1173–8211.
22. Uttarkar, S., Piontek, T., Dukare, S., Schomburg, C., Schlenke, P., Berdel, W.E., Müller-Tidow, C., Schmidt, T.J., Klempnauer, K.-H., Small-molecule disruption of the Myb/p300 cooperation targets acute myeloid leukemia cells. Mol. Cancer Ther. 15 (2016), 2905–2915.
23. Lane, M.D., Tang, Q.Q., Jiang, M.S., Role of the CCAAT enhancer binding proteins (C/EBPs) in adipocyte differentiation. Biochem. Biophys. Res. Commun. 266 (1999), 677–683.
24. Chayka, O., Kintscher, J., Braas, D., Klempnauer, K.-H., v-Myb mediates cooperation of a cell-specific enhancer with the mim-1 promoter. Mol. Cell. Biol. 25 (2005), 499–511.
25. Molvaersmyr, A.K., Saether, T., Gilfillan, S., Lorenzo, P.I., Kvaløy, H., Matre, V., Gabrielsen, O.S., A SUMO-regulated activation function controls synergy of c-Myb through a repressor-activator switch leading to differential p300 recruitment. Nucleic Acids Res. 38 (2010), 4970–4984.
26. Mink, S., Haenig, B., Klempnauer, K.-H., Interaction and functional collaboration of p300 and C/EBPβ. Mol. Cell. Biol. 17 (1997), 6609–6617.
27. Ivanova, O., Braas, D., Klempnauer, K.-H., Oncogenic point mutations in the Myb DNA-binding domain alter the DNA-binding properties of Myb at a physiological target gene. Nucleic Acids Res. 35 (2007), 7237–7247.
28. Steinmann, S., Coulibaly, A., Ohnheiser, J., Jakobs, A., Klempnauer, K.-H., Interaction and cooperation of the CCAAT-box enhancer-binding protein β (C/EBPβ) with the homeodomain-interacting protein kinase 2 (Hipk2). J. Biol. Chem. 288 (2013), 22257–22269.
29. Cao, Z., Umek, R.M., McKnight, S.L., Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 5 (1991), 1538–1552.
30. Krüppel, U., Müller-Schiffmann, A., Baldus, S.E., Smola-Hess, S., Steger, G., E2 and the co-activator p300 can cooperate in activation of the human papillomavirus type 16 early promoter. Virology 377 (2008), 151–159.
31. Jakobs, A., Steinmann, S., Henrich, S.M., Schmidt, T.J., Klempnauer, K.-H., Helenalin acetate, a natural sesquiterpene lactone with anti-inflammatory and anti-cancer activity, disrupts the cooperation of CCAAT-box/enhancer-binding protein beta (C/EBPβ) and co-activator p300. J. Biol. Chem. 291 (2016), 26098–26108.
32. Schwartz, C., Beck, K., Mink, S., Schmolke, M., Budde, B., Wenning, D., Klempnauer, K.-H., Recruitment of p300 by C/EBPbeta triggers phosphorylation of p300 and modulates coactivator activity. EMBO J. 22 (2003), 882–892.
33. Schomburg, C., Schuehly, W., Da Costa, F.B., Klempnauer, K.-H., Schmidt, T.J., Natural sesquiterpene lactones as inhibitors of Myb-dependent gene expression: structure-activity relationships. Eur. J. Med. Chem. 63 (2013), 313–320.
34. Hu, Y.L., Ramsay, R.G., Kanei-Ishii, C., Ishii, S., Gonda, T.J., Transformation by carboxyl-deleted Myb reflects increased transactivating capacity and disruption of a negative regulatory domain. Oncogene 6 (1991), 1549–1553.
35. Plachetka, A., Chayka, O., Wilczek, C., Melnik, S., Bonifer, C., Klempnauer, K.-H., C/EBPbeta induces chromatin opening at a cell-type-specifc enhancer. Mol. Cell. Biol. 28 (2008), 2102–2112.
36. Jakobs, A., Uttarkar, S., Schomburg, C., Steinmann, S., Coulibaly, A., Schlenke, P., Berdel, W.E., Müller-Tidow, C., Schmidt, T.J., Klempnauer, K.-H., An isoform-specific C/EBPβ inhibitor targets acute myeloid leukemia cells. Leukemia 30 (2016), 1612–1615.
37. Tang, Q.Q., Otto, T.C., Lane, M.D., CCAAT/enhancer-binding protein beta is required for mitotic clonal expansion during adipogenesis. Proc. Natl. Acad. Sci. U. S. A. 100 (2003), 850–855.
38. Otto, T.C., Lane, M.D., Adipose development: from stem cell to adipocyte. Crit. Rev. Biochem. Mol. Biol. 40 (2005), 229–242.
39. Vanden Berghe, W., Sabbe, L., Kaileh, M., Haegeman, G., Heyninck, K., Molecular insight in the multifunctional activities of Withaferin A. Biochem. Pharmacol. 84 (2012), 1282–1291.
40. Vyas, A.R., Singh, S.V., Molecular targets and mechanisms of cancer prevention and treatment by Withaferin A, a naturally occurring steroidal lactone. AAPS J. 16 (2014), 1–10.
41. Lee, I.C., Choi, B.Y., Withaferin-A-A natural anticancer agent with pleitropic mechanisms of action. Int. J. Mol. Sci., 17, 2016, E290.
42. Ozorowski, G., Ryan, C.M., Whitelegge, J.P., Luecke, H., Withaferin A binds covalently to the N-terminal domain of annexin A2. Biol. Chem. 393 (2012), 1151–1163.
43. Antony, M.L., Lee, J., Hahm, E.R., Kim, S.H., Marcus, A.I., Kumari, V., Ji, X., Yang, Z., Vowell, C.L., Wipf, P., Uechi, G.T., Yates, N.A., Romero, G., Sarkar, S.N., Singh, S.V.J., Growth arrest by the antitumor steroidal lactone Withaferin A in human breast cancer cells is associated with down-regulation and covalent binding at cysteine 303 of β-tubulin. J. Biol. Chem. 289 (2014), 1852–1865.
44. Bhaumik, P., Davis, J., Tropea, J.E., Cherry, S., Johnson, P.F., Miller, M., Structural insights into interactions of C/EBP transcriptional activators with the Taz2 domain of p300. Acta Crystallogr. D Biol. Crystallogr. 70 (2014), 1914–1921.
45. Sebastian, T., Johnson, P.F., Stop and go: anti-proliferative and mitogenic functions of the transcription factor C/EBPbeta. Cell Cycle 5 (2006), 953–957.
46. Sundfeldt, K., Ivarsson, K., Carlsson, M., Enerbäck, S., Janson, P.O., Brännström, M., Hedin, L., The expression of CCAAT/enhancer binding protein (C/EBP) in the human ovary in vivo: specific increase in C/EBPbeta during epithelial tumour progression. Br. J. Cancer 79 (1999), 1240–1248.
47. Rask, K., Thörn, M., Pontén, F., Kraaz, W., Sundfeldt, K., Hedin, L., Enerbäck, S., Increased expression of the transcription factors CCAAT-enhancer binding protein-beta (C/EBBeta) and C/EBzeta (CHOP) correlate with invasiveness of human colorectal cancer. Int. J. Cancer 86 (2000), 337–343.
48. Gomis, R.R., Alarcón, C., Nadal, C., Van Poznak, C., Massagué, J., C/EBPbeta at the core of the TGFbeta cytostatic response and its evasion in metastatic breast cancer cells. Cancer Cell 10 (2006), 203–214.
49. Regalo, G., Canedo, P., Suriano, G., Resende, C., Campos, M.L., Oliveira, M.J., Figueiredo, C., Rodrigues-Pereira, P., Blin, N., Seruca, R., Carneiro, F., Machado, J.C., C/EBPbeta is over-expressed in gastric carcinogenesis and is associated with COX-2 expression. J. Pathol. 210 (2006), 398–404.
50. Kim, M.H., Minton, A.Z., Agrawal, V., C/EBPbeta regulates metastatic gene expression and confers TNF-alpha resistance to prostate cancer cells. Prostate 69 (2009), 1435–1447.
51. Homma, J., Yamanaka, R., Yajima, N., Tsuchiya, N., Genkai, N., Sano, M., Tanaka, R., Increased expression of CCAAT/enhancer binding protein beta correlates with prognosis in glioma patients. Oncol. Rep. 15 (2006), 595–601.
52. Carro, M.S., Lim, W.K., Alvarez, M.J., Bollo, R.J., Zhao, X., Snyder, E.Y., Sulman, E.P., Anne, S.L., Doetsch, F., Colman, H., Lasorella, A., Aldape, K., Califano, A., Iavarone, A., The transcriptional network for mesenchymal transformation of brain tumours. Nature 463 (2010), 318–327.
53. Grogan, P.T., Sleder, K.D., Samadi, A.K., Zhang, H., Timmermann, B.N., Cohen, M.S., Cytotoxicity of Withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways. Investig. New Drugs, 31, 2013 (545-357).
54. Chang, E., Pohling, C., Natarajan, A., Witney, T.H., Kaur, J., Xu, L., Gowrishankar, G., D'Souza, A.L., Murty, S., Schick, S., Chen, L., Wu, N., Khaw, P., Mischel, P., Abbasi, T., Usmani, S., Mallick, P., Gambhir, S.S., AshwaMAX and Withaferin A inhibits gliomas in cellular and murine orthotopic models. J. Neuro-Oncol. 126 (2016), 253–264.