1H -NMR Metabolomics Study of the Effect of Cisplatin and Casiopeina IIgly on MDA-MB-231 Breast Tumor Cells

Abstract

The knowledge of the metabolic processes of designed metallodrugs for cancer treatment is an area that has been not profoundly studied. Casiopeina IIgly (CasIIgly), which belongs to the Casiopeínas® family, is a copper (II) coordination compound that has shown good biological activity against several cancer cells, low toxicity in normal cells, and antineoplastic activity in in vivo murine and xenografted models. In this work we employed a triple-negative highly metastatic breast carcinoma line (MDA-MB-231), which is one of the cancer types with a great mortality index, for 1H-NMR metabolomic analysis using cisplatin and CasIIgly, in order to quantify the effect of metallodrugs in the metabolic profile of this cell tumor line as a consequence of treatment at different times. Our findings indicate that cisplatin mainly contributes to phospholipid biosynthesis while CasIIgly affects processes such as carbohydrates and nucleotides metabolism. Also, we observed that CasIIgly treatment has an important and fast effect over MDA-MB-231 cell metabolism, which makes it a good alternative for treatment in this type of cancer.

Copper(II) Phenanthroline-Based Complexes as Potential AntiCancer Drugs: A Walkthrough on the Mechanisms of Action

“…These complexes have been extensively studied on both in vitro and in vivo models, showing that their anticancer activity is exerted through ROS accumulation that causes mitochondrial dysfunction, DNA damage and induces apoptosis [ 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. Some of these derivatives have been selected as candidates for Phase I clinical trials [ 48 , 49 , 50 ].…”

Impact of Conventional and Potential New Metal-Based Drugs on Lipid Metabolism in Osteosarcoma MG-63 Cells

“…Untargeted nuclear magnetic resonance (NMR) metabolomics has been applied to evaluate the metabolic impact of cDDP on several cancer cell lines, namely lung [19][20][21], brain [22][23][24], breast [25][26][27][28], ovarian [29] and OS [16,17,30,31]. Some of these studies analyzed whole or lysed cells, while others have focused on cellular extracts [18,23,24,28,29] and media [29]. As for OXA, to the best of the authors' knowledge, it has been assessed by NMR metabolomics of hydrophilic extracts of hepatocellular carcinoma [32] and OS [17] cells.…”

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

“…15,16 Several studies in the literature already exploited NMR metabolomics to evaluate the metabolic responses of cancer cells to metal based drugs, in particular Pt drugs. The effects of Cisplatin were studied in a variety of cancer cells including lung, 17 brain, [18][19][20] breast, 21,22 ovarian, 23,24 cancer cells, as well as osteosarcoma, 25,26 mostly by analyzing whole or lysed cells or focusing on cell extracts and cell media. Those studies revealed some common trends in the induced metabolic changes such as a direct effect on lipid metabolism and membrane integrity, a decrease of the overall metabolic activities of the treated cells, and the alteration of some other diagnostic metabolites e.g., UDP sugars.…”