A simple liposome assay for the screening of zinc ionophore activity of polyphenols

Investigating Structural Property Relationships to Enable Repurposing of Pharmaceuticals as Zinc Ionophores

“…Figure 4 suggests that quercetin is a more potent zinc ionophore than naringenin, requiring concentrations of 0.1 and 1 mM respectively to produce the responses shown. This has been confirmed previously in liposomal assays prepared via a different methodology where quercetin again demonstrated significantly greater ionophoric activity than naringenin [21,31]. The lack of a hydroxyl group on naringenin may confer weaker affinity for zinc and may explain this difference in effect.…”

“…Liposomes were synthesised according to a previously reported procedure [21,26], where 250 mg (3.289 × 10 −4 moles) 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and 1.4125 mg (3.65 × 10 −6 moles) cholesterol were dissolved in 8 mL chloroform and 4 mL of this solution was aliquoted into a 25 mL Round Bottom Flask (RBF). The solvent was then removed by rotary evaporation to obtain a thin film.…”

“…Screening of ionophores to transport ions across membranes will be assessed in model membranes using liposomes prepared by extrusion of 1-palmitoyl-2-oleoyl-sn-glycero-3phosphocholine. Liposomal systems are classic membrane mimetics; these systems are impermeable to ions [20] but can be loaded with ion sensitive fluorescent probes, such as FluoZin-3 (a zinc sensitive probe), which can detect zinc ions as they are transported across the cell membrane [21]. Pressman noted that ionophores will obey the Nernst equation [8] and, as such, the liposomal model may underestimate ionophoric effects, particularly in the cases of symport or antiport ionophoric mechanisms, as the ions needed to maintain equilibrium may not be present or indeed may be spent (i.e., transported to the other side of the membrane).…”

Resveratrol Potently Counteracts Quercetin Starvation‐Induced Autophagy and Sensitizes HepG2 Cancer Cells to Apoptosis

“…In consequence, it is feasible to hypothesize that, at the higher Zn +2 dose, some kind of polyphenol‐mediated effect/s on Zn +2 dynamics seem to be saturated; reactivating, in consequence, the autophagy process in HepG2, and decreasing the caspase‐3 cleavage. Interestingly, it has been previously shown that QCT can act as Zn +2 ionophore in Hepa cancer cells; and on the other hand, by using a liposome model it has also been shown that RSV and QCT are able to differentially modulate Zn +2 dynamics . Nevertheless, more experiments are needed to further clarify this interesting Zn +2 ‐mediated effect.…”

“…Interestingly, it has been previously shown that QCT can act as Zn +2 ionophore in Hepa cancer cells [59] ; and on the other hand, by using a liposome model it has also been shown that RSV and QCT are able to differentially modulate Zn +2 dynamics. [60] Nevertheless, more experiments are needed to further clarify this interesting Zn +2 -mediated effect.…”