Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Role of NADPH Oxidase-Mediated Generation of Reactive Oxygen Species in the Mechanism of Apoptosis Induced by Phenolic Acids in HePG2 Human Hepatoma Cells

  • Published : 2005.10.01
Download PDF
⟨ Previous Next ⟩

Abstract

Although plant-derived phenolic acids have been reported to have anti-cancer activity, the exact mechanism is not completely understood. In this study, we investigated the role for reactive oxygen species (ROS) as a mediator of the apoptosis induced by caffeic acid (CA) and ferulic acid (FA), common phenolic acids in plants in HepG2 human hepatoma cells. CA and FA reduced cell viability, and induced apoptotic cell death in a dose-dependent manner. In addition, they evoked a dose-related elevation of intracellular ROS. Treatment with various inhibitors of NADPH oxidase (diphenylene iodonium, apocynin, neopterine) significantly blunted both the generation of ROS and the induction of apoptosis induced CA and FA. These results suggest that ROS generated through activation of NADPH oxidase may play an essential role in the apoptosis induced by CA and FA in HepG2 cells. These results further suggest that CA and FA may be valuable for the therapeutic management of human hepatomas.

Keywords

References

  1. Babior, B. M., The respiratory burst oxidase. Curr. Opin. Hematol., 2, 55-60 (1995) https://doi.org/10.1097/00062752-199502010-00008
  2. Babior, B. M., NADPH oxidase: an update. Blood, 93, 1464-1476 (1999)
  3. Bhimani, R. S., Troll, W., Grunberger, D., and Frenkel, K., Inhibition of oxidative stress in HeLa cells by chemopreventive agents. Cancer Res., 53, 4528-4533 (1993)
  4. Bohler, T., Waiser, J., Hepburn, H., Gaedeke, J., Lehmann, C., Hambach, P., Budde, K, and Neumayer, H. H., TNF-and IL1-induce apoptosis in subconfluent rat mesangial cells. Evidence for the involvement of hydrogen peroxide and lipid peroxidation as second messengers. Cytokine, 12, 986-991 (2000) https://doi.org/10.1006/cyto.1999.0633
  5. Bombeli, T., Karsan, A., Tait, J. F., and Harlan, J. M., Apoptotic vascular endothelial cells become procoagulant. Blood, 89, 2429-2442 (1997)
  6. Chan, W. S., Wen, P. C., and Chiang, H. C., Structure-activity relationship of caffeic acid analogues on xanthine oxidase inhibition. Anticancer Res., 15, 703-707 (1995)
  7. Chiao, C., Carothers, A. M., Grunberger, D., Solomon, G., Preston, G. A., and Barrett, J. C., Apoptosis and altered redox state induced by caffeic acid phenethyl ester (CAPE) in transformed rat fibroblast cells. Cancer Res., 55, 3576-3583 (1995)
  8. Chung, T. W., Moon, S. K., Chang, Y. C., Ko, J. H., Lee, Y. C., Cho, G., Kim, S. H., Kim, J. G., and Kim, C. H., Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. FASEB J, 18, 1670-1681 (2004) https://doi.org/10.1096/fj.04-2126com
  9. Cool, R. H., Merten, E., Theiss, C., and Acker, H., Rac1, and not Rac2, is involved in the regulation of the intracellular hydrogen peroxide level in HepG2 cells. Biochem. J., 332, 5-8 (1998)
  10. Daniels, I., Lindsay, M. A., Keany, C. I., Burden, R. P., Fletcher, J., and Haynes, A. P., Role of arachidonic acid and its metabolites in thepriming of NADPH oxidase in human polymorphonuclear leukocytes by peritoneal dialysis effluent. Clin. Diagn. Lab. lmmunol., 5, 683-689 (1998)
  11. Ehleben, W., Porwol, T., Fandrey, J., Kummer, W., and Acker, H., Cobalt and desferrioxamine reveal crucial members of the oxygen sensing pathway in HepG2 cells. Kidney Int., 51, 483-491 (1997) https://doi.org/10.1038/ki.1997.67
  12. Fesen, M. R., Kohn, K. W., Leteurtre, F., and Pommier, Y., Inhibitors of human immunodeficiency virus integrase. Proc. Natl. Acad. Sci. U.S.A., 90, 2399-2403 (1993) https://doi.org/10.1073/pnas.90.6.2399
  13. Fleming, I. N., Elliott, C. M., Buchanan, F. G., Downes, C. P, and Exton, J. H., $Ca^{2+}$/calmodulin-dependent protein kinase II regulates Tiam1 by reversible protein phosphorylation. J. Biol. Chem., 274, 12753-12758 (1999) https://doi.org/10.1074/jbc.274.18.12753
  14. Frenkel, K., Wei, H., Bhimani, R., Ye, J., Zadunaisky, J. A., Huang, M. T., Ferraro, T., Conney, A. H., and Grunberger, D., Inhibition of tumor promoter-mediated processes in mouse skin and bovine lens by caffeic acid phenethyl ester. Cancer Res., 53, 1255-1261 (1993)
  15. Fujisawa, H., Regulation of the activities of multifunctional $Ca^{2+}$/calmodulin-dependent protein kinases. J. Biochem. (Tokyo), 129, 193-199 (2001) https://doi.org/10.1093/oxfordjournals.jbchem.a002843
  16. Galati, G., Sabzevari, O., Wilson, J. X., and O'Brien, P. J., Prooxidant activity and cellular effects of the phenoxyl radicals of dietary f1avonoids and other polyphenolics. Toxicology, 177, 91-104 (2002) https://doi.org/10.1016/S0300-483X(02)00198-1
  17. Graf, E., Antioxidant potential of ferulic acid. Free Radic. Biol. Med., 13, 435-448 (1992) https://doi.org/10.1016/0891-5849(92)90184-I
  18. Halliwell, B., Free radicals, reactive oxygen species and human disease: a critical evaluation with special reference to atherosclerosis. Br. J. Exp. Pathol., 70, 737-757 (1989)
  19. Huang, M. T., Ma, W., Yen, P., Xie, J. G., Han, J., Frenkel, K., Grunberger, D., and Conney, A. H., Inhibitory effects of caffeic acid phenethyl ester (CAPE) on 12-O-tetradecanoylphorbol13-acetate-induced tumor promotion in mouse skin and the synthesis of DNA, RNA, and protein in HeLa cells. Carcinogenesis, 17,761-765 (1996). https://doi.org/10.1093/carcin/17.4.761
  20. Jones, S. A., O'Donnell, V. B., Wood, J. D., Broughton, J. P., Hughes, E. J. and Jones, O. T., Expression of phagocyte NADPH oxidase components in human endothelial cells. Am. J. Physiol., 271, H1626-H1634 (1996)
  21. Kidd, V. J., Proteolytic activities that mediate apoptosis. Annu. Rev. Physiol., 60, 533-573 (1998) https://doi.org/10.1146/annurev.physiol.60.1.533
  22. Kojima, S., Nomura, T., Icho, T., Kajiwara, Y., Kitabatake, K., and Kubota, K., Inhibitory effect of neopterin on NADPH-dependent superoxide-generating oxidase of rat peritoneal macrophages. FEBS Lett., 329, 125-128 (1993) https://doi.org/10.1016/0014-5793(93)80207-B
  23. Kornblau, S. M., The role of apoptosis in the pathogenesis, prognosis, and therapy of hematologic malignancies. Leukemia, 12 Suppl 1, S41-S46 (1998)
  24. Koshihara, Y., Neichi, T., Murota, S., Lao, A., Fujimoto, Y., and Tatsuno, T., Caffeic acid is a selective inhibitor for leukotriene biosynthesis. Biochim. Biophys. Acta, 792, 92-97 (1984) https://doi.org/10.1016/0005-2760(84)90287-X
  25. Kummer, W. and Acker, H., Immunohistochemical demonstration of four subunits of neutrophil NAD(P)H oxidase in type I cells of carotid body. J. Appl. Physiol., 78, 1904-1909 (1995)
  26. LaBel, C. P., Ischiopoulos, H., and Bondy, S. C., Evaluation of the probe 2',7'-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem. Res. Toxicol., 5, 227-231 (1992) https://doi.org/10.1021/tx00026a012
  27. Lee, Y. S., Kang, Y. S., Lee, J. S., Nicolova, S., and Kim, J. A., Involvement of NADPH oxidase-mediated generation of reactive oxygen species in the apototic cell death by capsaicin in HepG2 human hepatoma cells. Free Radical Res., 8, 405-412 (2004)
  28. Lee, Y. S., Kang, Y. S., Lee, S. H., and Kim, J. A., Role of NAD(P)H oxidase in the tamoxifen-induced generation of reactive oxygen species and apoptosis In HepGL human hepatoblastoma cells. Cell Death Differ., 7, 925-932 (2000) https://doi.org/10.1038/sj.cdd.4400717
  29. Lowe, S. W. and Lin, A. W., Apoptosis in cancer. Carcinogenesis, 21, 485-495 (2000) https://doi.org/10.1093/carcin/21.3.485
  30. Marshall, C., Mamary, A. J., Verhoeven, A. J., and Marshall, B. E., Pulmonary artery NADPH oxidase is activated in hypoxic pulmonary vasoconstriction. Am. J. Respir. Cell Mol. Biol., 15, 633-644 (1996) https://doi.org/10.1165/ajrcmb.15.5.8918370
  31. Mathew, S. and Abraham, T. E., Ferulic acid: an antioxidant found naturally in plant cell walls and feruloyl esterases involved in its release and their applications. Crit. Rev. Biotechnol., 24, 59-83 (2004) https://doi.org/10.1080/07388550490491467
  32. Michaluart, P., Masferrer, J. L., Carothers, A. M., Subbaramaiah, K., Zweifel, B. S., Koboldt, C., Mestre, J. R., Grunberger, D., Sacks, P. G., Tanabe, T., and Dannenberg, A. J., Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation. Cancer Res., 59, 2347-2352 (1999)
  33. Mirzoeva, O. K., Yaqoob, P., Knox, K. A., and Calder, P. C., Inhibition of ICE-family cysteine proteases rescues murine lymphocytes from lipoxygenase inhibitor-induced apoptosis. FEBS Lett., 396, 266-270 (1996) https://doi.org/10.1016/0014-5793(96)01111-8
  34. Nardini, M., Leonardi, F., Scaccini, C., and Virgili, F., Modulation of ceramide-induced NF-kappaB binding activity and apoptotic response by caffeic acid in U937 cells: comparison with other antioxidants. Free Radical Biol. Med., 30, 722-733 (2001) https://doi.org/10.1016/S0891-5849(00)00515-3
  35. O'Donnell, B. V., Tew, D. G., Jones, O. T., and England, P. J., Studies on the inhibitory mechanism of iodonium compounds with special reference to neutrophil NADPH oxidase. Biochem. J., 290, 41-49 (1993)
  36. Rao, C. V., Desai, D., Simi, B., Kulkarni, N., Amin, S., and Reddy, B. S., Inhibitory effect of caffeic acid esters on azoxymethane-induced biochemical changes and aberrant crypt foci formation in rat colon. Cancer Res., 53, 4182-4188 (1993)
  37. Schiaffonati, L. and Tiberio, L., Gene expression in liver after toxic injury: analysis of heat shock response and oxidative stress-inducible genes. Liver, 17, 182-191 (1997)
  38. Schefferlie, J. G. and van Bladeren, P. J., In vitro and in vivo reversible and irreversible inhibition of rat glutathione Stransferase isoenzymes by caffeic acid and its 2-S-glutathionyl conjugate. Food Chem. Toxicol., 31, 475-482 (1993) https://doi.org/10.1016/0278-6915(93)90106-9
  39. Sergediene, E., Jonsson, K., Szymusiak, H., Tyrakowska, B., Rietjens, I. M., and Cenas, N., Prooxidant toxicity of polyphenolic antioxidants to HL-60 cells: description of quantitative structure-activity relationships. FEBS Lett., 462, 392-396 (1999) https://doi.org/10.1016/S0014-5793(99)01561-6
  40. Shahidi, F. and Naczk, M., Food phenolics. Sources, Chemistry, Effects, Applications, Technomic Publishing Company Inc., Lancaster (1995)
  41. Shen, H. M., Shi, C. Y., and Ong, C. N., Detection of elevated reactive oxygen species level in cultured rat hepatocytes treated with aflatoxin B1. Free Radical Biol. Med., 21, 139-146 (1996) https://doi.org/10.1016/0891-5849(96)00019-6
  42. Shiose, A. and Sumimoto, H., Arachidonic acid and phosphorylation synergistically induce a conformational change of $p47^{phox}$ to activate the phagocyte NADPH oxidase. J. Biol. Chem., 275, 13793-13801 (2000) https://doi.org/10.1074/jbc.275.18.13793
  43. Simon, H. U., Haj-Yehia, A., and Levi-Schaffer, F., Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis, 5, 415-418 (2000) https://doi.org/10.1023/A:1009616228304
  44. Song, Z. and Steller, H., Death by design: mechanism and control of apoptosis. Trends Cell Biol., 9, 49-52 (1999) https://doi.org/10.1016/S0962-8924(99)01670-0
  45. Stagos, D., Kazantzoglou, G., Magiatis, P., Mitaku, S., Anagnostopoulos, K., and Kouretas, D., Effects of plant phenolics and grape extracts from Greek varieties of Vitis vinifera on mitomycin C and topoisomerase I-induced nicking of DNA. lnt. J. Mol. Med., 15, 1013-1022 (2005)
  46. Stolk, J., Hiltermann, T. J., Dijkman, J. H., and Verhoeven, A J., Characteristics of the inhibition of NADPH oxidase activation in neutrophils by apocynin, a methoxy-substituted catechol. Am. J. Respir. Cell Mol. Biol., 11, 95-102 (1994) https://doi.org/10.1165/ajrcmb.11.1.8018341
  47. Suzukawa, K., Miura, K., Mitsushita, J., Resau, J., Hirose, K., Crystal, R., and Kamata, T., Nerve growth factor-induced neuronal differentiation requires generation of Rac1-regulated reactive oxygen species. J. Biol. Chem., 275, 13175-13178 (2000) https://doi.org/10.1074/jbc.275.18.13175
  48. Tanaka, T, Kojima, T, Kawamori, T, Yoshimi, N., and Mori, H., Chemoprevention of diethylnitrosamine-induced hepatocarcinogenesis by a simple phenolic acid protocatechuic acid in rats. Cancer Res., 53, 2775-2779 (1993)
  49. van Acker, S. A., van den Berg, D. J., Tromp, M. N., Griffioen, D. H., van Bennekom, W. P., van der Vijgh, W. J., and Bast, A., Structural aspects of antioxidant activity of flavonoids. Free Radical Biol. Med., 20, 331-342 (1996) https://doi.org/10.1016/0891-5849(95)02047-0
  50. van de Loosdrecht, A. .A, Nennie, E., Ossenkoppele, G. J., Beelen, R. H., and Langenhuijsen, M. M., Cell mediated cytotoxicity against U 937 cells by human monocytes and macrophages in a modified colorimetric MTT assay. A methodological study. J. Immunol. Methods, 141, 15-22 (1991) https://doi.org/10.1016/0022-1759(91)90205-T
  51. Vieira, O., Laranjinha, J., Madeira, V., and Almeida, L., Cholesteryl ester hydroperoxide formation in myoglobincatalyzed low density lipoprotein oxidation: concerted antioxidant activity of caffeic and p-coumaric acids with ascorbate. Biochem. Pharmacol., 55, 333-340 (1998) https://doi.org/10.1016/S0006-2952(97)00470-X
  52. Wang, T., Zhang, X., and Li, J. J., The role of $NF-{\kappa}B$ in the regulation of cell stress responses. Int. Immunopharmacol., 2, 1509-1520 (2002) https://doi.org/10.1016/S1567-5769(02)00058-9
  53. Wang, X. W., Role of p53 and apoptosis in carcinogenesis. Anticancer Res., 19, 4759-4771 (1999)
  54. Yamanaka, N., Oda, O., and Nagao, S., Prooxidant activity of caffeic acid, dietary non-flavonoid phenolic acid, on Cu2+-induced low density lipoprotein oxidation. FEBS Lett., 405, 186-190 (1997) https://doi.org/10.1016/S0014-5793(97)00185-3
  55. Youngson, C., Nurse, C., Yeger, H., Curnutte, J. T., Vollmer, C., Wong, V., and Cutz, E., Immunocytochemical localization on O2-sensing protein (NADPH oxidase) in chemoreceptor cells. Microsc. Res. Tech., 37, 101-106 (1997) https://doi.org/10.1002/(SICI)1097-0029(19970401)37:1<101::AID-JEMT10>3.0.CO;2-V
  56. Yu, B. P., Cellular defenses against damage from reactive oxygen species. Physiol. Rev., 74, 139-162 (1994)