Comparative NMR metabolomics of the responses of A2780 human ovarian cancer cells to clinically established Pt-based drugs

Ghini, Veronica; Magherini, Francesca; Massai, Lara; Messori, Luigi; Turano, Paola

doi:10.1039/d2dt02068h

Cited by 13 publications

(12 citation statements)

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“…18,19 It follows that the behaviour of these cytotoxic gold compounds largely differs from established anticancer platinum(II) drugs that were earlier reported to produce relatively modest metabolic alterations in the same cancer cell line, possibly due to their prevalent DNA damaging mechanism. 14 Finally, this study further demonstrates that NMR metabolomics is a powerful and effective tool to disclose the metabolic effects of anticancer metallodrugs offering the chance to establish valuable correlations between the main mechanistic aspects and the observed metabolic alterations.…”

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confidence: 66%

“…15 Moreover, in line with AF, both gold carbenes induce a signicant reduction of the UDP sugars (UDP-acetylglucosamine and UDP-galactosamine). Interestingly, a signicant decrement of these molecules was also observed in A2780 cells upon platinum drugs treatment 14 and was related to a reduction of cancer aggressiveness 16 and ER stress. 17 In conclusion, NMR metabolomics has revealed that these gold carbene compounds induce relevant and specic alterations in the cancer cell metabolome that are signicantly different from those induced by AF.…”

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confidence: 84%

“…11,12 Recently, we have implemented this investigative approach to characterise the metabolic perturbations induced by a few metallodrugs in a reference cancer cell line. 13,14…”

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confidence: 99%

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

et al. 2023

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confidence: 66%

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confidence: 84%

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

et al. 2023

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“…While carboplatin may share some of its antitumoral activity with oxaliplatin, it also has specific mechanisms of action and yields negligible neurotoxicity. 16,17 Hence, the use of carboplatin-containing chemotherapy could be relevant in patients with advanced PDAC, as previously reported in combination with gemcitabine, 18 and in other pancreatic neoplasms including neuroendocrine carcinomas 19 and mucinous cystadenocarcinomas. 20 The aim of this study was to report the efficacy and tolerance of the LV5FU2-carboplatin combination in a large and comprehensive consecutive cohort patients with advanced PDAC after failure of standard chemotherapies.…”

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confidence: 78%

Efficacy and tolerance of LV5FU2-carboplatin chemotherapy in patients with advanced pancreatic ductal adenocarcinoma after failure of standard regimens

et al. 2023

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Background: Chemotherapy options in patients with advanced pancreatic ductal adenocarcinoma (PDAC) after failure of standard chemotherapies are limited. Objectives: We aimed to report the efficacy and safety of the leucovorin and 5-fluorouracil (LV5FU2) and carboplatin combination in this setting. Design: We performed a retrospective study including consecutive patients with advanced PDAC who received LV5FU2–carboplatin between 2009 and 2021 in an expert center. Methods: We measured overall survival (OS) and progression-free survival (PFS), and explored associated factors using Cox proportional hazard models. Results: In all, 91 patients were included (55% male, median age 62), with a performance status of 0/1 in 74% of cases. LV5FU2–carboplatin was mainly used in third (59.3%) or fourth line (23.1%), with three (interquartile range: 2.0–6.0) cycles administered on average. The clinical benefit rate was 25.2%. Median PFS was 2.7 months (95% CI: 2.4–3.0). At multivariable analysis, no extrahepatic metastases ( p = 0.083), no ascites or opioid-requiring pain ( p = 0.023), <2 prior treatment lines ( p < 0.001), full dose of carboplatin ( p = 0.004), and treatment initiation >18 months after initial diagnosis ( p < 0.001) were associated with longer PFS. Median OS was 4.2 months (95% CI: 3.48–4.92) and was influenced by the presence of extrahepatic metastases ( p = 0.058), opioid-requiring pain or ascites ( p = 0.039), and number of prior treatment lines (0.065). Prior tumor response under oxaliplatin did not impact either PFS or OS. Worsening of preexisting residual neurotoxicity was infrequent (13.2%). The most common grade 3–4 adverse events were neutropenia (24.7%) and thrombocytopenia (11.8%). Conclusion: Although the efficacy of LV5FU2–carboplatin appears limited in patients with pretreated advanced PDAC, it may be beneficial in selected patients.

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“…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

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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.

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Comparative NMR metabolomics of the responses of A2780 human ovarian cancer cells to clinically established Pt-based drugs

Abstract: Pt-based drugs play a very important role in current cancer treatments; yet, their cellular and mechanistic aspects are not fully understood. NMR metabolomics provides a powerful tool to investigate the...

Cited by 13 publications

References 50 publications

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

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

Efficacy and tolerance of LV5FU2-carboplatin chemotherapy in patients with advanced pancreatic ductal adenocarcinoma after failure of standard regimens

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

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