Novel Antiproliferative Biphenyl Nicotinamide: NMR Metabolomic Study of its Effect on the MCF-7 Cell in Comparison with Cisplatin and Vinblastine

Abstract

A 1H-NMR-based metabolomic study was performed on MCF-7 cell lines treated with a novel nicotinamide derivative (DT-8) in comparison with two drugs characterized by a well-established mechanism of action, namely the DNA-metalating drug cisplatin (cis-diamminedichloridoplatinum(II), CDDP) and the antimitotic drug vinblastine (vinblastine, VIN). The effects of the three compounds, each one at the concentration corresponding to the IC50 value, were investigated, with respect to the controls (K), by the 1H-NMR of cells lysates and multivariate analysis (MVA) of the spectroscopic data. Relevant differences were found in the metabolic profiles of the different treatments with respect to the controls. A large overlap of the metabolic profiles in DT-8 vs. K and VIN vs. K suggests a similar biological response and mechanism of action, significantly diverse with respect to CDDP. On the other hand, DT8 seems to act by disorganizing the mitotic spindle and ultimately blocking the cell division, through a mechanism implying methionine depletion and/or S-adenosylmethionine (SAM) limitation.

1H-NMR metabolomic profile of healthy and osteoarthritic canine synovial fluid before and after UC-II supplementation

“…The relative change in discriminating metabolite content between the observed groups was evaluated by analyzing the mean values ± standard deviation of selected bucket-reduced distinctive unbiased NMR signals after spectra normalization. In particular, the changes in metabolite levels between two groups were calculated as the log2-FC ratio of the normalized median intensity of the corresponding signals in the spectra of the groups 66 , 67 . Statistical significance was set at least at an adjusted p value < 0.05.…”

Metabolic characterisation of transglutaminase 2 inhibitor effects in breast cancer cell lines

“…Several recent metabolomics studies have been performed on MDA-MB-231 and MCF-7 cell lines to test the effects of different anticancer treatments [42,43,46,47,49,65].…”

“…In this context, we analysed the impact of the TG2 inhibitors NC9 and AA9 on two BrCa cell lines, the hormone-sensitive MCF-7 and the hormone-independent MDA-MB-231, the latter characterised by a more aggressive phenotype and a higher level of TG2 expression [26]. Previous metabolomic studies on these cell lines revealed changes in the concentration of many metabolites after exposure to several drugs or other treatments [40][41][42][43][44][45][46][47][48].…”

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

“…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, 18–20 breast, 21,22 and 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. These studies revealed some common trends in the induced metabolic changes such as a direct effect on lipid metabolism and membrane integrity, a decrease in the overall metabolic activities of the treated cells, and the alteration of some other diagnostic metabolites, e.g.…”