International Journal of Hematology

, Volume 92, Issue 1, pp 136–143

Ellagic acid, a natural polyphenolic compound, induces apoptosis and potentiates retinoic acid-induced differentiation of human leukemia HL-60 cells

  • Yuki Hagiwara
  • Takashi Kasukabe
  • Yasuhiko Kaneko
  • Nozomi Niitsu
  • Junko Okabe-Kado
Original Article


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.


Ellagic acid Acute myeloid leukemia cells Apoptosis Caspase Differentiation ATRA 


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Copyright information

© The Japanese Society of Hematology 2010

Authors and Affiliations

  • Yuki Hagiwara
    • 1
    • 2
  • Takashi Kasukabe
    • 1
  • Yasuhiko Kaneko
    • 1
  • Nozomi Niitsu
    • 2
  • Junko Okabe-Kado
    • 1
  1. 1.Research Institute for Clinical OncologySaitama Cancer CenterKitaadachi-gunJapan
  2. 2.Department of Hematology, Comprehensive Cancer Center, International Medical CenterSaitama Medical UniversityHidakaJapan

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