Cellular and molecular alterations induced by low-dose fisetin in human chronic myeloid leukemia cells

The present study aimed to evaluate the cellular and molecular effects of low concentrations of the flavonoid, fisetin, on K562 human chronic myeloid leukemia cells, in the context of both potential anti-proliferative and anti-metastatic effects. Thiazolyl blue tetrazolium bromide assay, Trypan blue exclusion assay, Annexin V/propidium iodide test, cell cycle analysis, Transwell migration and invasion assays, the fluorescence staining of β-catenin and F-actin as well as reverse transcription-quantitative polymerase chain reaction were performed to achieve the research goal. Furthermore, the nature of the interaction between fisetin and arsenic trioxide in the K562 cells was analyzed according to the Chou-Talalay median-effect method. We found that low concentrations of fisetin had not only a negligible effect on the viability and apoptosis of the K562 cells, but also modulated the mRNA levels of selected metastatic-related markers, accompanied by an increase in the migratory and invasive properties of these cancer cells. Although some markers of cell death were significantly elevated in response to fisetin treatment, these were counterbalanced through anti-apoptotic and pro-survival signals. With decreasing concentrations of fisetin and arsenic trioxide, the antagonistic interactions between the 2 agents increased. On the whole, the findings of this study suggest that careful consideration should be taken when advising cancer patients to take fisetin as a dietary supplement and when considering fisetin as a potential candidate for the treatment of chronic myeloid leukemia. Further more detailed studies are required to confirm our findings.