Abstract
The therapeutic approach to acute myeloid leukemia (AML) is usually chemotherapy, but severe side effects and complications induced by the anticancer drugs are sometimes fatal and are major problems in the clinical setting. Recently, more specifically targeted agents have been developed for the treatment of AML; however, most candidate agents for targeted therapy have yet to be translated into clinical application. Natural compounds appear to be safer than the current chemotherapeutic agents. Recently, it has been reported that reactive oxygen species (ROS) produced by natural compounds such as (−)-epigallocatechin-3-gallate (EGCG) induce apoptosis in myeloid leukemic cells. EGCG markedly induced apoptosis of myeloperoxidase (MPO)-positive myeloid leukemic cells. Treatment with EGCG caused a significant ROS production in MPO-positive leukemic cells. ROS are now thought of as signaling molecules in response to various extracellular stimuli. On the other hand, ROS may be the direct mediator of EGCG-induced apoptosis in myeloid leukemic cells. In particular, highly toxic ROS such as hydroxyl radical (·OH) generated via the H2O2/MPO halide system may directly mediate oxidative stress-induced apoptosis in myeloid leukemic cells.
Similar content being viewed by others
References
Tallman MS, Gilliland DG, Rowe JM (2005) Drug therapy for acute myeloid leukemia. Blood 106:1154–1163
Weick JK, Kopecky KJ, Appelbaum FR et al (1996) A randomized investigation of high-dose cytarabine in induction in acute myeloid leukemia. Blood 88:2841–2851
Cassileth PA, Harrington DP, Appelbaum FR et al (1998) Chemotherapy compared with autologous bone-marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med 339:1649–1656
Harousseau JL, Cahn JY, Pignon B et al (1997) Comparison of autologous bone marrow transplantation and intensive therapy as postremission therapy in adult acute myeloid leukemia. Blood 90:2978–2986
Estey E (2004) Clinical trials in AML of the elderly: should we change our methodology? Leukemia 18:1772–1774
Appelbaum FR, Gundacker HM, Head DR et al (2006) Age and acute myeloid leukemia. Blood 107:3481–3485
Buchner T, Berdel WE, Wormann B et al (2005) Treatment of older patients with AML. Crit Rev Oncol Hematol 56:247–259
Smith SM, Le Beau MM, Huo D et al (2003) Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood 102:43–52
Gojo I, Karp JE (2001) The impact of biology on the treatment of secondary AML. Cancer Treat Res 108:231–255
Levine EG, Bloomfield CD (1992) Leukemias and myelodysplastic syndromes secondary to drug, radiation, and environmental exposure. Semin Oncol 19:47–84
Kantarjian H, O’Brien S, Cortes J et al (2006) Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer 106:1090–1098
Huang ME, Ye YC, Chen SR et al (1998) Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 72:567–572
Grignani F, Valtieri M, Gabbianelli M et al (2000) PML/RARα fusion protein expression in normal human hematopoietic progenitors dictates myeloid commitment and the promyelocytic phenotype. Blood 96:1531–1537
Tallman MS, Nabhan C, Feusner JH et al (2002) Acute promyelocytic leukemia: evolving therapeutic strategies. Blood 99:759–767
Bullinger L, Dohner K, Bair E et al (2004) Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia. N Engl J Med 350:1605–1616
Valk PJ, Verhaak RG, Beijen MA et al (2004) Prognostically useful gene- expression profiles in acute myeloid leukemia. N Engl J Med 350:1617–1628
Grimwade D, Haferlach T (2004) Gene expression profiling in acute myeloid leukemia. N Engl J Med 350:1676–1678
Ley TJ, Minx PJ, Walter MJ et al (2003) A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes. Proc Natl Acad Sci U S A 100:14275–14280
Goldman JM, Melo JV (2001) Targeting the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344:1084–1086
Kizaki M, Ueno H, Yamazoe Y et al (1996) Mechanisms of retinoid resistance in leukemic cells: possible role of cytochrome P450 and P-glycoprotein. Blood 87:725–733
Takayama N, Kizaki M, Hida T et al (2001) Novel mutation in the PML/RARα chimeric gene exhibits dramatically decreased ligand-binding activity and confers acquired resistance to retinoic acid in acute promyelocytic leukemia. Exp Hematol 29:864–872
Gorre ME, Mohammed M, Ellwood K et al (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293:876–880
Papa S, Skulachev VP (1997) Reactive oxygen species, mitochondria, apoptosis and aging. Mol Cell Biochem 174:305–319
Allen RG, Tresini M (2000) Oxidative stress and gene regulation. Free Radic Biol Med 28:463–499
Chapple IL (1997) Reactive oxygen species and antioxidants in inflammatory diseases. J Clin Periodontol 24:287–296
Sauer H, Wartenberg M, Hescheler J (2001) Reactive oxygen species as intracellular messengers during cell growth and differentiation. Cell Physiol Biochem 11:173–186
Finkel T (2003) Oxidant signals and oxidative stress. Curr Opin Cell Biol 15:247–254
Herr I, Debatin KM (2001) Cellular stress response and apoptosis in cancer therapy. Blood 98:2603–2614
Bigelow DJ, Squier TC (2005) Redox modulation of cellular signaling and metabolism through reversible oxidation of methionine sensors in calcium regulatory proteins. Biochem Biophys Acta 1703:121–134
Buttke TM, Sandstrom PA (1994) Oxidative stress as a mediator of apoptosis. Immunology Today 15:7–10
Jacobson MD (1996) Reactive oxygen species and programmed cell death. Trends Biochem Sci 21:83–86
Clutton S (1997) The importance of oxidative stress in apoptosis. Br Med Bull 53:662–668
Ueda S, Masutani H, Nakamura H et al (2002) Redox control of cell death. Antioxid Redox Signal 4:405–414
Tobiume K, Matsuzawa A, Takahashi T et al (2001) ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep 2:222–228
Nakazato T, Ito K, Miyakawa Y et al (2005) Catechin, a green tea component, rapidly induces apoptosis of myeloid leukemic cells via modulation of reactive oxygen species production in vitro and inhibits tumor growth in vivo. Haematologica 90:317–325
Lea MA, Xiao Q, Sadhukhan AK et al (1996) Inhibitory effects of tea extracts and (−)-epigallocatechin gallate on DNA synthesis and proliferation of hepatoma and erythroleukemia cells. Cancer Lett 68:231–236
Islam S, Islam N, Kermode T et al (2000) Involvement of caspase-3 in epigallocatechin-3-gallate-mediated apoptosis of human chondrosarcoma cells. Biochem Biophys Res Commun 270:793–797
Ahmad N, Feyes DK, Nieminen AL et al (1997) Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J Natl Cancer Inst 89:1881–1886
Bertolini F, Fusetti L, Cinieri S et al (2000) Inhibition of angiogenesis and induction of endothelial and tumor cell apoptosis by green tea in animal models of human high-grade non-Hodgkin's lymphoma. Leukemia 14:1477–1482
Pisters KMW, Newman RA, Coldman B et al (2001) Phase I trial of oral green tea extract in adult patients with solid tumors. J Clin Oncol 19:1830–1838
Chow H-HS, Cai Y, Alberts DS et al (2001) Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol Biomark Prev 10:53–58
Nakagawa H, Hasumi K, Woo JT et al (2004) Generation of hydrogen peroxide primarily contributes to the induction of Fe(II)-dependent apoptosis in Jurkat cells by (−)-epigallocatechin gallate. Carcinogenesis 25:1567–1574
Hampton MB, Kettle AJ, Winterbourn CC (1998) Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 92:3007–3017
Bruno JG, Herman TS, Cano VL et al (1999) Selective cytotoxicity of 3-amino-l-tyrosine correlates with peroxidase activity. In Vitro Cell Biol Anim 35:376–382
Wagner BA, Buettner GR, Oberley LW et al (2000) Myeloperoxidase is involved in H2O2-induced apoptosis of HL-60 human leukemia cells. J Biol Chem 275:22461–22469
Nakazato T, Sagawa M, Yamato K et al (2007) Myeloperoxidase (MPO) is a key regulator of oxidative stress-mediated apoptosis in myeloid leukemia. Clin Cancer Res 13:5436–5445
Kowaltowski AJ, Vercesi AE (1999) Mitochondrial damage induced by conditions of oxidative stress. Free Radic Biol Med 26:463–471
Ren JG, Xia HL, Just T et al (2001) Hydroxyl radical-induced apoptosis in human tumor cells is associated with telomere shortening but not telomerase inhibition and caspase activation. FEBS Lett 19:123–132
Setsukinai K, Urano Y, Kakinuma K et al (2002) Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species. J Biol Chem 278:3170–3175
Matsuo T, Cox C, Bennett JM (1989) Prognostic significance of myeloperoxidase positivity of blast cells in acute myeloblastic leukemia without maturation (FAB: M1): an ECOG study. Hematol Pathol 3:153–158
Suic M, Boban D, Markovic-Glamocak M et al (1992) Prognostic significance of cytochemical analysis of leukemic M2 blasts. Med Oncol Tumor Pharmacother 9:41–45
Matsuo T, Kuriyama K, Miyazaki Y et al (2003) The percentage of myeloperoxidase-positive blast cells is a strong independent prognostic factor in acute myeloid leukemia, even in the patients with normal karyotype. Leukemia 17:1538–1543
Acknowledgements
I thank Dr. Tomonori Nakazato and members of the Kizaki laboratory for their excellent experiments, helpful discussion, and assistance. This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
Conflict of interest statement
No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kizaki, M. Biological significance of myeloperoxidase (MPO) on green tea component, (−)-epigallocatechin-3-gallate (EGCG)-induced apoptosis: its therapeutic potential for myeloid leukemia. Targ Oncol 3, 45–50 (2008). https://doi.org/10.1007/s11523-007-0065-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11523-007-0065-2