| Summary: | Flavonoids are natural polyphenolic compounds with desired bio-functions but with chemical instability and sensitivity to temperature, oxygen, and other factors. Apigenin and luteolin, two flavones of the flavonoid family in plant foods, were; thus, assessed and compared for their stability, especially the changes in anti-cancer activity in response to the conducted heat treatments and the addition of ferrous or cupric ions. The two flavones in aqueous solutions showed first-order degradation at 20 and 37 °C. The addition of ferrous or cupric ions (except for Cu<sup>2+</sup> at 37 °C) enhanced luteolin stability via forming the luteolin−metal complexes; however, Fe/Cu addition (especially at 37 °C) consistently impaired apigenin stability. Using the human cervical cancer Hela cells and two cell treatment times (24 and 48 h), it was evident that heat treatments (37 and 100 °C) or Fe/Cu addition could endow apigenin and luteolin with decreased activities in growth inhibition, DNA damage, intracellular reactive oxygen species (ROS) generation, and apoptosis induction. In general, higher temperature led to greater decrease in these activities, while Fe<sup>2+</sup> was more effective than Cu<sup>2+</sup> to decrease these activities. The correlation analysis also suggested that the decreased ROS generation of the two flavones in the Hela cells was positively correlated with their decreased apoptosis induction. It is; thus, concluded that the two treatments can influence the two flavones’ stability and especially exert an adverse impact on their anti-cancer activities.
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