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

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Abstract

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.

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Acknowledgments

This work was partially supported by a Grant-in-Aid for Scientific Research (18591091) from Japan Society for the Promotion of Science and a Grant-in-Aid for Third Term Comprehensive Control Research for Cancer from the Ministry of Health, Labor and Welfare of Japan.

Conflict of interest statement

We declare no competing financial interests.

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Authors and Affiliations

  1. Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan

    Yuki Hagiwara, Takashi Kasukabe, Yasuhiko Kaneko & Junko Okabe-Kado

  2. Department of Hematology, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan

    Yuki Hagiwara & Nozomi Niitsu

Authors
  1. Yuki Hagiwara
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  2. Takashi Kasukabe
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  5. Junko Okabe-Kado
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Correspondence to Junko Okabe-Kado.

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Hagiwara, Y., Kasukabe, T., Kaneko, Y. et al. Ellagic acid, a natural polyphenolic compound, induces apoptosis and potentiates retinoic acid-induced differentiation of human leukemia HL-60 cells. Int J Hematol 92, 136–143 (2010). https://doi.org/10.1007/s12185-010-0627-4

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  • DOI: https://doi.org/10.1007/s12185-010-0627-4

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