Ellagic acid, a natural polyphenolic compound, induces apoptosis and potentiates retinoic acid-induced differentiation of human leukemia HL-60 cells
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All-trans retinoic acid (ATRA) is a standard drug used for differentiation therapy in acute promyelocytic leukemia. To potentiate this therapy, we examined the effect of ellagic acid (EA), a natural polyphenolic compound with antiproliferative and antioxidant properties, on the growth and differentiation of HL-60 acute myeloid leukemia cells. EA was found to induce apoptosis, which was blocked by pan-caspase inhibitor, Z-VAD-FMK. EA activated the caspase-3 pathway and enhanced the expressions of myeloid differentiation markers (CD11b, MRP-14 protein, granulocytic morphology) induced by ATRA treatment. These results indicate that EA is a potent apoptosis inducer and also effectively potentiates ATRA-induced myeloid differentiation of HL-60 cells.
- Tallman MS, Gilliland DG, Rowe JM. Drug therapy for acute myeloid leukemia. Blood. 2005;106:1154–63. CrossRef
- Honma Y. Cotylenin A—a plant growth regulator as a differentiation inducing agent against myeloid leukemia. Leuk Lymphoma. 2002;43(6):1169–78. CrossRef
- Dorai T, Aggarwal BB. Role of chemopreventive agents in cancer therapy. Cancer Lett. 2004;215:129–40. CrossRef
- Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, Heber D. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem. 2005;16:360–7. CrossRef
- Stoner GD, Mukhtar H. Polyphenols as cancer chemopreventive agents. J Cell Biochem Suppl. 1995;22:169–80. CrossRef
- Festa F, Aglitti T, Duranti G, Ricordy R, Perticone P, Cozzi R. Strong antioxidant activity of ellagic acid in mammalian cells in vitro revealed by the comet assay. Anticancer Res. 2001;21(6A):3903–8.
- Banzouzi JT, Prado R, Menan H, Valenin A, Roumestan C, Mallie M, Pellissier Y, Blache Y. In vitro antiplasmodial activity of extracts of Alchornea cordifolia and identification of an active constituent: ellagic acid. J Ethnopharmacol. 2002;81(3):399–401. CrossRef
- Aiyer HS, Vadhanam MV, Stoyanova R, Caprio GD, Clapper ML, Gupta RC. Dietary berries and ellagic acid prevent oxidative DNA damage and modulate expression of DNA repair genes. Int J Mol Sci. 2008;9(3):327–41. CrossRef
- Han DH, Lee MJ, Kim JH. Antioxidant and apoptosis-inducing activities of ellagic acid. Anticancer Res. 2006;26(5A):3601–6.
- Losso JN, Bansode RR, Trappey A 2nd, Bawadi HA, Truax R. In vitro anti-proliferative activities of ellagic acid. J Nutr Biochem. 2004;15(11):672–8. CrossRef
- Edderkaoui M, Odinokova I, Ohno I, Gukovsky I, Go VL, Pandol SJ, Gukovskaya AS. Ellagic acid induces apoptosis through inhibition of nuclear factor kappa B in pancreatic cancer cells. World J Gastroenterol. 2008;14(23):3672–80. CrossRef
- Li TM, Chen GW, Su CC, Yeh CC, Cheng KC, Chung JG. Ellagic acid induced p53/p21 expression, G1 arrest and apoptosis in human bladder cancer T24 cells. Anticancer Res. 2005;25(2A):971–9.
- Larrosa M, Thomás-Barberán FA, Espín JC. The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathway. J Nutr Biochem. 2006;17(9):611–25. CrossRef
- Narayanan BA, Geoffroy O, Willingham MC, Re GG, Nixon DW. p53/p21 (WAF1/CIP1) expression and its possible role of in G1 arrest and apoptosis in ellagic acid treated cancer cells. Cancer Lett. 1999;136(2):215–21. CrossRef
- Mertens-Talcott SU, Talcott ST, Percival SS. Low concentrations of quercetin and ellagic acid synergistically influence proliferation, cytotoxicity and apoptosis in MOLT-4 human leukemia cells. J Nutr. 2003;133(8):2669–74.
- Nuňez G, Benedict MA, Hu Y, Inohara N. Caspases: the proteases of the apoptotic pathway. Oncogene. 1998;17(25):3237–45.
- Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science. 1998;281(5381):1305–8. CrossRef
- Ashkenazi A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer. 2002;2(6):420–30. CrossRef
- 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(2):155–62. CrossRef
- Lawrence D, Shahrokh Z, Marsters S, Achilles K, Shih D, Mounho B, et al. Differential hepatocyte toxicity of recombinant Apo2L/TRAIL versions. Nat Med. 2001;7(4):383–5. CrossRef
- Gazitt Y. TRAIL is a potent inducer of apoptosis in myeloma cells derived from multiple myeloma patients and is not cytotoxic to hematopoietic stem cells. Leukemia. 1999;13(11):1817–24. CrossRef
- Pollack IF, Erff M, Ashkenazi A. Direct stimulation of apoptotic signaling by soluble Apo2L/tumor necrosis factor-related apoptosis-inducing ligand leads to selective killing of glioma cells. Clin Cancer Res. 2001;7(5):1362–9.
- Qin J, Chaturvedi V, Bonish B, Nickoloff BJ. Avoiding premature apoptosis of normal epidermal cells. Nat Med. 2001;7(4):385–6. CrossRef
- Ashkenazi A, Holland P, Eckhardt SG. Ligand-based targeting of apoptosis in cancer: the potential of recombinant human apoptosis ligand 2/tumor necrosis factor-related apoptosis-inducing ligand (rhApo2L/TRAIL). J Clin Oncol. 2008;26(21):3621–30. CrossRef
- Fjaeraa C, Nånberg E. Effect of ellagic acid on proliferation, cell adhesion and apoptosis in SH-SY5Y human neuroblastoma cells. Biomed Pharmacother. 2009;63(4):254–61. CrossRef
- Castaigne S, Chomienne C, Daniel MT, Ballerini P, Berqer R, Fenaux P, Deqos L. All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood. 1990;76(9):1704–9.
- Yokoyama A, Okabe-Kado J, Wakimoto N, et al. Evaluation by multivariate analysis of the differentiation inhibitory factor nm23 as a prognostic factor in acute myelogenous leukemia and application to other hematological malignancies. Blood. 1998;91:1845–51.
- Rumjahn SM, Javed MA, Wong N, Law WE, Buxton ILO. Purinergic regulation of angiogenesis by human breast carcinoma-secreted nucleoside diphosphate kinase. Br J Cancer. 2007;97:1372–80. CrossRef
- Khanduja KL, Avti PK, Kumar S, Mittal N, Sohi KK, Pathak CM. Anti-apoptotic activity of caffeic acid, ellagic acid and ferulic acid in normal human peripheral blood mononuclear cells: a Bcl-2 independent mechanism. Biochem Biophys Acta. 2006;1760(2):283–9.
- Tasaki M, Uemura T, Maeda M, Ishii Y, Okamura T, Inoue T, et al. Safety assessment of ellagic acid, a food additive, in a subchronic toxicity study using F344 rats. Food Chem Toxicol. 2008;46(3):1119–24.
- Ellagic acid, a natural polyphenolic compound, induces apoptosis and potentiates retinoic acid-induced differentiation of human leukemia HL-60 cells
International Journal of Hematology
Volume 92, Issue 1 , pp 136-143
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Ellagic acid
- Acute myeloid leukemia cells
- Industry Sectors
- Author Affiliations
- 1. Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan
- 2. Department of Hematology, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan