The effects of two cytotoxic gold(<scp>i</scp>) carbene compounds on the metabolism of A2780 ovarian cancer cells: mechanistic inferences through NMR analysis

Ghini, Veronica; Mannelli, Michele; Massai, Lara; Geri, Andrea; Zineddu, Stefano; Gamberi, Tania; Messori, Luigi; Turano, Paola

doi:10.1039/d3ra04032a

Cited by 6 publications

(4 citation statements)

References 19 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this context, our research group is carrying out a comparative NMR metabolomic study to analyze the responses of A2780 human ovarian cancer cells to a panel of selected gold(I) compounds, previously characterized with good anticancer properties. The obtained results for auranofin [31] and two carbene molecules [33] were published in 2020 and 2023, respectively. Interestingly, the treatment with the three compounds affects the metabolome of A2780 cells in different ways.…”

Section: Nmr Metabolomics and Metal-based Compounds: State-of-the-artmentioning

confidence: 99%

“…The gold monocarbene and dicarbene complexes behave differently from auranofin but display many alterations in common between the two of them; however, the latter amplifies the effects. Glycolysis is significantly affected and both drugs also caused a reduced uptake of several amino acids [33].…”

Section: Nmr Metabolomics and Metal-based Compounds: State-of-the-artmentioning

confidence: 99%

“…• Au(NHC)ClInorganics 2024, 12, x FOR PEER REVIEW 6 of 16[33] • Au(NHC)Cl Human ovarian cancer A2780 cells1H NMR • Cell lysates • Growth media IC50 at 72h 6, 12, 24 h • [Au(NHC)2]PF6 [17] [(p-cymene)6Ru6 • Human ovarian cancer 1 H HR-MAS Intact cells IC50 at 96 h 24, 72 h • [Au(NHC) 2 ]PF 6 Inorganics 2024, 12, x FOR PEER REVIEW 6 of 16 [33] • Au(NHC)Cl Human ovarian cancer A2780 cells 1 H NMR • Cell lysates • Growth media IC50 at 72h 6, 12, 24 h • [Au(NHC)2]PF6 PPh2)(Cl2)Ru(ŋ 6 -p-cymene) (GA113) Human melanoma A375 cells 1 H NMR Cell extracts (m/c) IC50 at 24 h 24 h [17] [(p-cymene)6Ru6 • Human ovarian cancer 1 H HR-MAS Intact cells IC50 at 96 h 24, 72 h Inorganics 2024, 12, x FOR PEER REVIEW 6 of 16[33] • Au(NHC)Cl…”

mentioning

confidence: 99%

See 2 more Smart Citations

Cell Metabolomics to Guide the Design of Metal-Based Compounds

Ghini

2024

Inorganics

Self Cite

View full text Add to dashboard Cite

Despite the increasing interest in the development of novel metal-based compounds for cancer treatment, these molecules are currently poorly characterized in mechanistic terms, due to their multiple macromolecular targets inside the cells. In this review, we show how 1H NMR metabolomics provides a powerful tool to investigate the metabolic perturbations induced by metal-compounds in cells. The chemical identity and concentration of metabolites detected in cell lysates and their respective growth media by NMR can be viewed as a global fingerprint that describes the response to drug treatment. In this framework, the applications of NMR-based metabolomics to study cellular effects induced by the treatment of cells with anticancer metal-based compounds are comprehensively reviewed.

show abstract

Section: Nmr Metabolomics and Metal-based Compounds: State-of-the-artmentioning

confidence: 99%

Section: Nmr Metabolomics and Metal-based Compounds: State-of-the-artmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Cell Metabolomics to Guide the Design of Metal-Based Compounds

Ghini

2024

Inorganics

Self Cite

View full text Add to dashboard Cite

show abstract

“…As an example, some of us characterized the cellular effects induced in A2780 cells and A2780cis cells by treatment with the three clinically established platinum drugs, i.e., cisplatin, carboplatin, and oxaliplatin [21]. With the same methodological approach, we also addressed the cellular alterations caused by gold(I)-based drugs with optimal anticancer properties [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

NMR Metabolomics of Primary Ovarian Cancer Cells in Comparison to Established Cisplatin-Resistant and -Sensitive Cell Lines

Ghini,

Sorbi,

Fambrini

et al. 2024

Cells

Self Cite

View full text Add to dashboard Cite

Cancer cell lines are frequently used in metabolomics, such as in vitro tumor models. In particular, A2780 cells are commonly used as a model for ovarian cancer to evaluate the effects of drug treatment. Here, we compare the NMR metabolomics profiles of A2780 and cisplatin-resistant A2780 cells with those of cells derived from 10 patients with high-grade serous ovarian carcinoma (collected during primary cytoreduction before any chemotherapeutic treatment). Our analysis reveals a substantial similarity among all primary cells but significant differences between them and both A2780 and cisplatin-resistant A2780 cells. Notably, the patient-derived cells are closer to the resistant A2780 cells when considering the exo-metabolome, whereas they are essentially equidistant from A2780 and A2780-resistant cells in terms of the endo-metabolome. This behavior results from dissimilarities in the levels of several metabolites attributable to the differential modulation of underlying biochemical pathways. The patient-derived cells are those with the most pronounced glycolytic phenotype, whereas A2780-resistant cells mainly diverge from the others due to alterations in a few specific metabolites already known as markers of resistance.

show abstract

Unlocking the Power of Human Ferritin: Enhanced Drug Delivery of Aurothiomalate in A2780 Ovarian Cancer Cells

Cosottini,

Geri,

Ghini

et al. 2024

Angewandte Chemie

View full text Add to dashboard Cite

Aurothiomalate (AuTM) is an FDA‐approved antiarthritic gold drug with unique anticancer properties. To enhance its anticancer activity, we prepared a bioconjugate with human apoferritin (HuHf) by attaching some AuTM moieties to surface protein residues. The reaction of apoferritin with excess AuTM yielded a single adduct, that was characterized by ESI MS and ICP‐OES analysis, using three mutant ferritins and trypsinization experiments. The adduct contains ~3 gold atoms per ferritin subunit, arranged in a small cluster bound to Cys90 and Cys102. MD simulations provide a plausible structural model for the cluster. The adduct was evaluated for its pharmacological properties and was found to be significantly more cytotoxic than free AuTM against A2780 cancer cells mainly due to higher gold uptake. NMR‐metabolomics showed that AuTM bound to HuHf and free AuTM induced qualitatively similar changes in treated cancer cells, indicating that the effects on cell metabolism are approximately the same, in agreement with independent biochemical experiments. In conclusion, we have demonstrated here that a molecularly precise bioconjugate formed between AuTM and HuHf exhibits anticancer properties far superior to the free drug, while retaining its key mechanistic features. Evidence is provided that human ferritin can serve as an excellent carrier for this metallodrug.

show abstract

The effects of two cytotoxic gold(i) carbene compounds on the metabolism of A2780 ovarian cancer cells: mechanistic inferences through NMR analysis

Abstract: The changes in the exo- and endo-metabolome of A2780 ovarian cancer cells caused by two cytotoxic gold carbene compounds were monitored via1H NMR.

Cited by 6 publications

References 19 publications

Cell Metabolomics to Guide the Design of Metal-Based Compounds

Cell Metabolomics to Guide the Design of Metal-Based Compounds

NMR Metabolomics of Primary Ovarian Cancer Cells in Comparison to Established Cisplatin-Resistant and -Sensitive Cell Lines

Unlocking the Power of Human Ferritin: Enhanced Drug Delivery of Aurothiomalate in A2780 Ovarian Cancer Cells

Contact Info

Product

Resources

About