Ellagic acid, a natural polyphenolic compound, induces apoptosis and potentiates retinoic acid-induced differentiation of human leukemia HL-60 cells.
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.
Hagiwara
Yuki
Y
Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama, Japan.
Kasukabe
Takashi
T
Kaneko
Yasuhiko
Y
Niitsu
Nozomi
N
Okabe-Kado
Junko
J
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D004357:Drug Synergism; D004610:Ellagic Acid / Q000494:pharmacology*; D005419:Flavonoids; D018922:HL-60 Cells; D006801:Humans; D010636:Phenols; D059808:Polyphenols; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D004610:Ellagic Acid; D014212:Tretinoin