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Updated: Jun 4, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Cytotoxicity of apigenin on leukemia cell lines: implications for prevention and therapy
R R Ruela-de-Sousa1, G M Fuhler, N Blom
1Department of Biochemistry, Biology Institute, University of Campinas, Campinas, São Paulo, Brazil.
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.
Insights
The dietary flavonoid apigenin shows anticancer effects by halting leukemia cell growth. However, it may reduce chemotherapy effectiveness, particularly in erythroid leukemia, by inducing cell cycle arrest and autophagy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Natural compounds offer potential for cancer prevention and treatment.
- The mechanisms of action for many natural compounds, including flavonoids, are not fully understood.
- Apigenin, a common dietary flavonoid, has demonstrated anticancer properties.
Purpose of the Study:
- To investigate the molecular effects of apigenin on myeloid and erythroid leukemia cell lines.
- To determine if apigenin influences leukemia cell proliferation, cell cycle, apoptosis, and autophagy.
- To assess the impact of apigenin on leukemia cell sensitivity to chemotherapy.
Main Methods:
- Treatment of HL60 (myeloid) and TF1 (erythroid) leukemia cell lines with apigenin.
- Analysis of cell cycle progression using flow cytometry.
- Investigation of signaling pathways, including JAK/STAT and PI3K/PKB.
- Assessment of apoptosis via caspase activation.
- Evaluation of autophagy initiation.
- Testing of cell sensitivity to vincristine.
Main Results:
- Apigenin inhibited proliferation in both HL60 and TF1 cells by inducing cell cycle arrest (G2/M in HL60, G0/G1 in TF1).
- Apigenin targeted the JAK/STAT pathway in both cell types.
- In HL60 cells, apigenin inhibited the PI3K/PKB pathway and induced apoptosis.
- In TF1 cells, apigenin induced autophagy but not apoptosis, leading to reduced sensitivity to vincristine.
Conclusions:
- Apigenin exhibits chemopreventive potential by arresting leukemia cell cycles.
- Apigenin's effects vary by leukemia subtype, potentially impacting chemotherapy efficacy.
- Dietary intake of apigenin during leukemia treatment warrants caution due to potential interference with therapeutic agents.
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