Implicación de NF-κB y p53 en la expresión de receptores de muerte-TRAIL y apoptosis por procianidinas en células metastásicas humanas SW620

María Elena Maldonado, Souad Bousserouel, Francine Gossé, Annelise Lobstein, Francis Raul, .

Palabras clave: apoptosis, neoplasias colorrectales, flavonoides, proteína p53 supresora de tumor, receptores del ligando inductor de apoptosis relacionado con el FNT

Resumen

Introducción. Se ha demostrado que el factor nuclear-κB y p53 aumentan los mediadores proapoptósicos como los receptores de muerte TRAIL-DR4/-DR5, según el estímulo y el tipo celular. Previamente demostramos que las procianidinas de manzana aumentaban la expresión de TRAIL-DR4/-DR5, superando la resistencia a TRAIL característica en células humanas metastásicas SW620 derivadas del cáncer de colon.
Objetivo. Investigar si NF-κB y p53 están involucrados en la apoptosis inducida por procianidinas en las células SW620.
Materiales y métodos. La muerte celular y las proteínas p53, TRAIL-DR4/-DR5 se analizaron por citometría de flujo. Los ARN mensajeros (ARNm) de DR4/DR5 se analizaron por RT-PCR. Las formas activadas de p50/p65 y p53 se estudiaron por ELISA e inmunodetección.
Resultados. La muerte celular activada por procianidinas fue prevenida por inhibidores específicos de NF-κB y de p53: amino-4-(4-fenoxi-feniletilamino)-quinazolina y pifitrina α, respectivamente. La quinazolina y la pifitrina α inhibieron la activación dependiente de procianidinas de TRAIL-DR4/DR5. Sin embargo, el aumento en la expresión de TRAIL-DR4 disminuyó significativamente sólo cuando la quinazolina y la pifitrina α se usaron simultáneamente; este efecto no se observó con cada uno por separado. No se observaron para TRAIL-DR5 estos efectos, lo cual sugiere que la expresión de cada receptor de muerte TRAIL puede estar regulada en forma diferente.
Conclusiones. Estos datos sugieren que NF-κB y p53 se requieren parcialmente en la apoptosis de células SW620 inducida por procianidinas mediante el aumento en TRAIL-DR4/-DR5. La proporción de DR4/DR5 podría ser un factor determinante en la activación de la apoptosis por vía de TRAIL-DR4/-DR5.

Descargas

La descarga de datos todavía no está disponible.
  • María Elena Maldonado INSERM U682, Laboratory of Nutritional Cancer Prevention, Strasbourg, France Faculty of Medicine, University Louis Pasteur, Strasbourg, France Institut de Recherche contre les Cancers de l’Appareil Digestif (IRCAD), Strasbourg, France
  • Souad Bousserouel INSERM U682, Laboratory of Nutritional Cancer Prevention, Strasbourg, France Faculty of Medicine, University Louis Pasteur, Strasbourg, France
  • Francine Gossé INSERM U682, Laboratory of Nutritional Cancer Prevention, Strasbourg, France Faculty of Medicine, University Louis Pasteur, Strasbourg, France
  • Annelise Lobstein CNRS UMR7081, Faculty of Pharmacy, University Louis Pasteur, Illkirch, France
  • Francis Raul INSERM U682, Laboratory of Nutritional Cancer Prevention, Strasbourg, France Faculty of Medicine, University Louis Pasteur, Strasbourg, France

Referencias bibliográficas

1. Sethi G, Sung B, Aggarwal BB. Nuclear factor-κB activation: from bench to bedside. Exp Biol Med. 2008;233:21-31.
2. Shishodia S, Aggargarwal BB. Nuclear factor-kB: A friend or a foe in cancer? Biochem Pharmacol. 2004;68:1071-80.
3. Ravi R, Bedi GC, Engstrom LW, Zeng Q, Mookerjee B, Gélinas C. Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-κB. Nat Cell Biol. 2001;3:409-16.
4. Begg AA, Sha WC, Bronson RT, Ghosh S, Baltimore D. Embryonic lethality and liver degeneration in mice lacking the Rel A component of NF-κB. Nature. 1995;376:167-70.
5. Begg AA, Baltimore D. An essential role for NF-κB in preventing TNF-α induced cell death. Science. 1996;274:782-4.
6. van Antwerd DJ, Martin SJ, Kafri T, Green DR, Verma IM. Suppression of TNF-α induced apoptosis by NF-κB. Science. 1996;274:787-9.
7. Liv ZG, Hsu H, Gorddel DV, Karin M. Dissection of the TNF receptor I effector functions. JNK activation in not linked to apoptosis while NF-κB activation prevents cell death. Cell. 1996;87:565-76.
8. Wang CY, Mayo MW, Baldwin Jr AS. TNF-α and cancer therapy-induced apoptosis: potentiation by inhibition of NF-κB. Science. 1996;274:784-7.
9. Ryan KM, Ernst MK, Rice NR, Vousden KH. Role of NF-kB in p53-mediated programmed cell death. Nature. 2000;404:892-7.
10. Baetu TM, Kwon H, Sharma S, Grandvaux N, Hiscott J. Disruption of NF-kappaB signaling reveals a novel role for NF-kappaB in the regulation of TNF-related apoptosis-inducing ligand expression. J Immunol. 2001;167:3164-73.
11. Siegmund D, Hausser A, Peters N, Scheurich P, Wajant H. Tumor necrosis factor (TNF) and phorbol ester induce TNF-related apoptosis-inducing ligand (TRAIL) under critical involvement of NF-kappa B essential modulator (NEMO)/IKKgamma. J Biol Chem. 2001;76:43708-12.
12. Kwon D, Choi K, Choi C, Benveniste EN. Hydrogen peroxide enhances TRAIL-induced cell death through up-regulation of DR5 in human astrocytic cells. Biochem Biophys Res Commun. 2008;372:870-4.
13. Grimm T, Schneider S, Naschberger E, Huber J, Guenzi E, Kieser A, et al. EBV latent membrane protein-1 protects B cells from apoptosis by inhibition of BAX. Blood. 2005;15:3263-9.
14. Henson ES, Gibson EM, Villanueva J, Bristow NA, Haney N, Gibson SB. Increased expression of Mcl-1 is responsible for the blockage of TRAIL-induced apoptosis mediated by EGF/ErbB1 signaling pathway. J Cell Biochem. 2003;89:1177-92.
15. Ruiz C, Ruiz-Ruiz C, Rodríguez A, Ortiz-Ferrón G, Redondo JM, López-Rivas A. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) decoy receptor TRAIL-R3 is up-regulated by p53 in breast tumor cells through a mechanism involving an intronic p53-binding site. J Biol Chem. 2004;279:4093-101.
16. Takimoto R, El-Deiry WS. Wild-type p53 transactivates the KILLER/DR5 gene through an intronic sequence-specific DNA-binding site. Oncogene. 2000;19:1735-43.
17. Chen JJ, Chou CW, Chang YF, Chen CC. Proteasome inhibitors enhance TRAIL-induced apoptosis through the intronic regulation of DR5: Involvement of NF-κB and reactive oxygen species-mediated p53 activation. J Immunol. 2008;180:8030-9.
18. Muller M, Wilder S, Bannasch D, Israeli D, Lehlbach K, Li-Weber M, et al. p53 activates the CD95 (APO-1/Fas) gene in response to DNA damage by anticancer drugs. J Exp Med. 1998;188:2033-45.
19. Wu GS, Burns TF, McDonald III ER, Jiang W, Meng R, Krantz ID, et al. KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat Genet. 1997;17:141-3.
20. Halaby MJ, Yang DQ. p53 translational control: a new facet of p53 regulation and its implication for tumorigenesis and cancer therapeutics. Gene. 2007;395:1-7.
21. Millau JF, Bastien N, Drouin R. P53 transcriptional activities: A general overview and some thoughts. Mutat Res. 2008;681:118-33.
22. Liu X, Yue P, Khuri FR, Sun SY. p53 upregulates death receptor 4 expression through an intronic p53 binding site. Cancer Res. 2004;64:5078-83.
23. Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, et al. Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 1999;104:155-62.
24. Gossé F, Guyot S, Roussi S, Lobstein AL, Fischer B, Seiler N, et al. Chemopreventive properties of apple procyanidins on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis. Carcinogenesis. 2005;26:1291-5.
25. Barth SW, Fahndrich C, Bub A, Dietrich H, Watzl B, Will F, et al. Cloudy apple juice decreases DNA damage, hyperproliferation and aberrant crypt foci development in the distal colon of DMH-initiated rats. Carcinogenesis. 2005;26:1414-21.
26. Barth SW, Faehndrich C, Bub A, Watzl B, Will F, Dietrich H, et al. Cloudy apple juice is more effective than apple polyphenols and an apple juice derived cloud fraction in a rat model of colon carcinogenesis. J Agric Food Chem. 2007;55:1181-7.
27. Ohkami H, Tazawa K, Yamashita I, Shimizu T, Murai K, Kobashi K, et al. Effects of apple pectin on fecal bacterial enzymes in azoxymethane-induced rat colon carcinogenesis. Jpn J Cancer Res. 1995;86:523-9.
28. Pan L, Zessner H, Will F, Klimo K, Frank N, Dietrich H, et al. Natural cloudy apple juice and a polyphenol-enriched apple juice extract prevent intestinal adenoma formation in the App (Min/+) model for colon cancer prevention. Cancer Epidemiol Biomarkers Prev. 2005;14:2715s.
29. Mandir N, Englyst H, Goodlad RA. Resistant carbohydrates stimulate cell proliferation and crypt fission in wild-type mice and in the Apc mouse model of intestinal cancer, association with enhanced polyp development. Br J Nutr. 2008;100:711-21.
30. Renard C, Dupont N, Guillermin P. Concentrations and characteristics of procyanidins and other phenolics in apples during fruit growth. Phytochem. 2007;68:1128-38.
31. Auger C, Al-Awwadi N, Bornet A, Rouanet JM, Gasc F, Cros G, et al. Catechins and procyanidins in mediterranean diets. Food Res Int. 2004;37:233-45.
32. Terry P, Giovannucci E, Michels KB, Bergkvist L, Hansen H, Holmberg L, et al. Fruit, vegetables, dietary fiber, and risk of colorectal cancer. J Natl Cancer Inst. 2001;93:525-33.
33. Ramos S. Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. J Nutr Biochem. 2007;18:427-42.
34. Maldonado-Celis ME, Roussi S, Foltzer-Jourdainne C, Gossé F, Lobstein A, Habold C, et al. Modulation by polyamines of apoptotic pathways triggered by procyanidins in human metastatic SW620 cells. Cell Mol Life Sci. 2008;65:1425-34.
35. Maldonado-Celis ME, Bousserouel S, Gossé F, Minker C, Lobstein C, Raul F. Differential induction of apoptosis by apple procyanidins in TRAIL-sensitive human colon tumor cells and derived TRAIL-resistant metastatic cells. J Cancer Mol. 2009;5:21-30.
36. Souquet JM, Labarbe B, Le Guerneve C, Cheynier V, Moutounet M. Phenolic composition of grape stems. J Agric Food Chem. 2000;48:1076-80.
37. Guyot S, Marnet N, Sanoner P, Drilleau JF. Direct thiolysis on crude apple materials for high-performance liquid chromatography characterization and quantification of polyphenols in cider apple tissues and juices. Methods Enzymol. 2001;335:57-70.
38. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C[T]) method. Methods. 2001;25:402-8.
39. Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods. 1991;139:271-9.
40. Rodrigues NR, Rowan A, Smith ME, Kerr IB, Bodmer WF, Gannon JV, et al. p53 mutations in colorectal cancer. Proc Natl Acad Sci USA. 1990;87:7555-9.
41. Huerta S, Heinzerling JH, Anguiano-Hernández Y-M, Huerta-Yepez S, Lin J, Chen D, et al. Modification of gene products involved in resistance to apoptosis in metastatic colon cancer cells: Roles of Fas, Apaf-1, NFκB, IAPs, Smac/DIABLO, and AIF. J Surg Res. 2007;142:184-94.
42. Shetty S, Graham BA, Brown JG, Hu X, Vegh-Yarema N, Harding G, et al. Transcription factor NF-κB differentially regulates death receptor 5 expression involving histone deacetylase. Mol Cell Biol. 2005;25:5404-16.
43. Farhana L, Dawson MI, Fontana JA. Apoptosis induction by a novel retinoid-related molecule requires nuclear factor-kappaB activation. Cancer Res. 2005;65:4909-17.
44. Li L, Rao JN, Bass BL, Wang JY. NF-κB activation and susceptibility to apoptosis after polyamine depletion in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2001;280:G992-1004.
45. Pfeffer LM, Yang CH, Murti A, McCormack SA, Viar MJ, Ray RM, et al. Polyamine depletion induces rapid NF-κB activation in IEC-6 cells. J Biol Chem. 2001;276:45909-13.
46. Guan B, Yue P, Lotan R, Sun SY. Evidence that the human death receptor 4 is regulated by activator protein 1. Oncogene. 2002;21:3121-9.
47. Kim YH, Park JW, Lee JY, Kwon TK. Sodium butyrate sensitizes TRAIL-mediated apoptosis by induction of transcription from the DR5 gene promoter through Sp1 sites in colon cancer cells. Carcinogenesis. 2004;25:1813-20.
Cómo citar
Maldonado, M. E., Bousserouel, S., Gossé, F., Lobstein, A., & Raul, F. (2010). Implicación de NF-κB y p53 en la expresión de receptores de muerte-TRAIL y apoptosis por procianidinas en células metastásicas humanas SW620. Biomédica, 30(4), 577-86. https://doi.org/10.7705/biomedica.v30i4.296
Publicado
2010-12-01
Sección
Artículos originales