Abstract
Background: The insensitivity of cancer cells to therapeutic agents is considered to be the main cause of failure of therapy and mortality of patients with cancer. A particularly important problem in these patients is the phenomenon of multidrug resistance, consisting of abnormal, elevated expression of transport proteins (ABC family). The aim of this research included determination of IC50 values of selected furanocoumarins in the presence and absence of mitoxantrone in leukemia cells and analysis of changes in apoptosis using anexinV/IP and Casp3/IP after 24 h exposure of cell lines to selected coumarins in the presence and absence of mitoxantrone in IC50 concentrations. Methods: Research was conducted on 3 cell lines derived from the human hematopoietic system: HL-60, HL-60/MX1 and HL-60/MX2. After exposure to coumarin compounds, cells were subjected to cytometric analysis to determine the induction of apoptosis by two methods: the Annexin V test with propidium iodide and the PhiPhiLux-G1D2 reagent containing caspase 3 antibodies. Results: All of the furanocoumarin derivatives studied were found to induce apoptosis in leukemia cell lines. Conclusions: Our results clearly show that the furanocoumarin derivatives are therapeutic substances with antitumor activity inducing apoptosis in human leukemia cells with phenotypes of resistance.
Highlights
Coumarins are a group of biologically active compounds that are produced by living organisms as secondary metabolites
Diverse dose-dependent cytotoxicity of the IC50 (and IC50 (+C) cells of the three cancer cell lines exposed to coumarin derivatives were the subject of our previous work [17]
All furanocoumarin derivatives investigated by us induce apoptotic death in the cells of the tested lines HL60, HL60/MX1 and HL60/MX2
Summary
Coumarins are a group of biologically active compounds that are produced by living organisms (plants, fungi and bacteria) as secondary metabolites. They are of great interest among researchers as coumarin agents possess numerous pharmacological properties including anti-inflammatory, antithrombotic, antibacterial, antifungal, antiviral, anti-hypertensive, anticonvulsant and anticancer, among others [1,2,3,4,5]. Furanocoumarins, in particular, have a strong antiproliferative effect, inhibiting the growth of cancer cells by modifying several molecular pathways, such as regulation of the signal transducer and activator of transcription 3, nuclear factor-kB, phosphatidylinositol-3-kinase/AKT and mitogenactivated protein kinase expression [7]. The insensitivity of cancer cells to therapeutic agents is considered to be the main cause of failure of therapy and mortality of patients with cancer. The aim of this research included determination of IC50 values of selected furanocoumarins in the presence and absence of mitoxantrone in leukemia cells and analysis of changes in apoptosis using anexinV/IP and Casp3/IP after 24 h exposure of cell lines to selected coumarins in the presence and absence of mitoxantrone in IC50 concentrations
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