Assessing flavones’ selective modulation of cell signalling in acute myeloid leukaemia and non-cancerous cells in vitro [Presentation]

Acute myeloid leukaemia (AML) is a rising age-related problem in developed countries. Disrupted cell signalling pathways promote leukaemic cell survival, increase in cellular proliferation and leukaemogenesis. Established chemotherapeutics like the anthracycline doxorubicin (Dox) demonstrate adverse side effects in patients. Flavones such as baicalein (BL) can offer a sustainable plant-based adjuvant with research suggesting anticancer properties and favourable safety without serious adverse side effects.
Screening of flavones binding to apoptosis proteins associated with AML was performed in silico. In vitro assays in the AML model MOLM-13 and the B-lymphocyte cell line RPMI1788 were used to assess the effective concentrations of Dox and three flavones (BL, FL1, and FL2). CyQuant-based assays have been optimised to measure cytotoxicity over 48h with varying concentration of the tested compounds.
In silico results predicted the optimal binding conformations of flavones to apoptosis-related proteins. For both cell lines, a dose-dependent relationship was observed between cell viability and Dox treatments (0.039 μM - 2.5 μM) with AML-MOLM-13 showing 1.5-fold lower IC50 (=0.034 μM; p=0.0262) than non-cancer-RPMI1788 (IC50=0.050 μM). For the flavones (1.25 μM – 80/100 μM) in MOLM-13, FL1 and FL2 demonstrated dose-dependent cytotoxicity; which in BL was observed if concentration > 10 μM. In RPMI1788 dose-dependent cytotoxicity was observed if [flavone]> 20 μM. BL was 3-fold more cytotoxic (p<0.0001) in MOLM-13 (IC50=19 μM) than RPMI1788(IC50=59 μM). Similarly, for FL1, MOLM-13 was 8-fold more sensitive (IC50=9 μM; p<0.0001) to the flavone than RPMI1788 (IC50=72 μM). FL2 demonstrated IC50=11 μM in MOLM-13, but in RPMI1788 the FL2 did not reduce the viability below 68%.
The results suggest that plant-based flavones may selectively inhibit AML over non-cancerous cells in vitro. By using plant-based compounds, this research promotes social sustainability in healthcare, aligning with UN's SDGs 3 (Good Health and Well-being), 12 (Responsible Consumption and Production), and 15 (Life on Land). Further studies will be employed to assess the structure-related activities and drug combinations. Using in vitro and in silico methods, future work will aim to
evaluate the cell cycle and signalling pathways such as apoptosis, autophagy, and Wnt to understand the mechanism of action at protein, genetic and epigenetic level.
References
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