Cytotoxicity of apigenin on leukemia cell lines: implications for prevention and therapy.

Abstract:

:Natural-food-based compounds show substantial promise for prevention and biotherapy of cancers including leukemia. In general, their mechanism of action remains unclear, hampering rational use of these compounds. Herein we show that the common dietary flavonoid apigenin has anticancer activity, but also may decrease chemotherapy sensitivity, depending on the cell type. We analyzed the molecular consequences of apigenin treatment in two types of leukemia, the myeloid and erythroid subtypes. Apigenin blocked proliferation in both lineages through cell-cycle arrest in G(2)/M phase for myeloid HL60 and G(0)/G(1) phase for erythroid TF1 cells. In both cell lines the JAK/STAT pathway was one of major targets of apigenin. Apigenin inhibited PI3K/PKB pathway in HL60 and induced caspase-dependent apoptosis. In contrast, no apoptosis was detected in TF1 cells, but initiation of autophagy was observed. The block in cell cycle and induction of autophagy observed in this erythroleukemia cell line resulted in a reduced susceptibility toward the commonly used therapeutic agent vincristine. Thus, this study shows that although apigenin is a potential chemopreventive agent due to the induction of leukemia cell-cycle arrest, caution in dietary intake of apigenin should be taken during disease as it potentially interferes with cancer treatment.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Ruela-de-Sousa RR,Fuhler GM,Blom N,Ferreira CV,Aoyama H,Peppelenbosch MP

doi

10.1038/cddis.2009.18

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

e19

issn

2041-4889

pii

cddis200918

journal_volume

1

pub_type

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