Investigation of the cytotoxic implications of metal chelators against melanoma and approaches to improve the cytotoxicity profiles of metal coordinating agents

Akladios, Fady N.; Andrew, Scott D.; Parkinson, C. J.

doi:10.1007/s10534-016-9945-1

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…Finally, another study has shown that a different class of metal chelators (i.e. thiosemicarbazones) have the ability to induce cytotoxicity on melanoma cells by disrupting the cellular antioxidant defence system thus causing elevation of intracellular ROS levels [74].…”

Section: Discussionmentioning

confidence: 99%

Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

et al. 2019

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The anticancer activity of a series of novel synthesized, hydroxypyridone-based metal chelators (analogues of L-mimosine) was evaluated in an in vitro model of melanoma consisting of malignant melanoma (A375), non-melanoma epidermoid carcinoma (A431) and immortalized non-malignant keratinocyte (HaCaT) cells. More specifically, we have demonstrated that the L-enantiomer of a methylated analogue of L-mimosine (compound 22) can exert a potent anticancer effect in A375 cells when compared to either A431 or HaCaT cells. Moreover, we have demonstrated that this analogue has the ability to i) promote increased generation of reactive oxygen species (ROS), ii) activate both intrinsic and extrinsic apoptosis and iii) induce perturbations in cell cycle growth arrest. Our data highlights the potential of compound 22 to act as a promising therapeutic agent against an in vitro model of human malignant melanoma.

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Section: Discussionmentioning

confidence: 99%

Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

et al. 2019

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“…On the other hand, it has been reported that Dp44mT and their complexes with iron and copper cause apoptosis by generating cytotoxic ROS [ 23 , 40 ]. Moreover, Akladios et al reported that in some TSC, the addition of metal cations may increase activity [ 41 , 42 ]. This observation led to the alternative use of TSC as ionophores.…”

Section: Introductionmentioning

confidence: 99%

The role of oxidative stress in activity of anticancer thiosemicarbazones

et al. 2018

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Thiosemicarbazones are chelators of transition metals such as iron or copper whose anticancer potency is intensively investigated. Although two compounds from this class have entered clinical trials, their precise mechanism of action is still unknown. Recent studies have suggested the mobilization of the iron ions from a cell, as well as the inhibition of ribonucleotide reductase, and the formation of reactive oxygen species. The complexity and vague nature of this mechanism not only impedes a more rational design of novel compounds, but also the further development of those that are highly active that are already in the preclinical phase. In the current work, a series of highly active thiosemicarbazones was studied for their antiproliferative activity in vitro. Our experiments indicate that these complexes have ionophoric properties and redox activity. They appeared to be very effective generating reactive oxygen species and deregulating the antioxidative potential of a cell. Moreover, the genes that are responsible for antioxidant capacity were considerably deregulated, which led to the induction of apoptosis and cell cycle arrest. On the other hand, good intercalating properties of the studied compounds may explain their ability to cleave DNA strands and to also poison related enzymes through the formation of reactive oxygen species. These findings may help to explain the particularly high selectivity that they have over normal cells, which generally have a stronger redox equilibrium.

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“…Therefore, DMSO − water mixtures are widely used in biological studies serving as a proper solvent for several biomolecules such as flavins, carotene, etc. (Akladios et al 2016 ; Rajniak et al 2018 ; Tsai et al 2018 ). However, the possibility of iron complexation by the solvent ligands is normally not considered in these studies.…”

Section: Introductionmentioning

confidence: 99%

Revealing the nuclearity of iron citrate complexes at biologically relevant conditions

Gracheva,

Klencsár,

Homonnay

et al. 2023

Biometals

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Citric acid plays an ubiquitous role in the complexation of essential metals like iron and thus it has a key function making them biologically available. For this, iron(III) citrate complexes are considered among the most significant coordinated forms of ferric iron that take place in biochemical processes of all living organisms. Although these systems hold great biological relevance, their coordination chemistry has not been fully elucidated yet. The current study aimed to investigate the speciation of iron(III) citrate using Mössbauer and electron paramagnetic resonance spectroscopies. Our aim was to gain insights into the structure and nuclearity of the complexes depending on the pH and iron to citrate ratio. By applying the frozen solution technique, the results obtained directly reflect the iron speciation present in the aqueous solution. At 1:1 iron:citrate molar ratio, polynuclear species prevailed forming most probably a trinuclear structure. In the case of citrate excess, the coexistence of several monoiron species with different coordination environments was confirmed. The stability of the polynuclear complexes was checked in the presence of organic solvents.

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Investigation of the cytotoxic implications of metal chelators against melanoma and approaches to improve the cytotoxicity profiles of metal coordinating agents

Cited by 4 publications

References 37 publications

Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

The role of oxidative stress in activity of anticancer thiosemicarbazones

Revealing the nuclearity of iron citrate complexes at biologically relevant conditions

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