Impact of the Pd(2)Spm (Spermine) Complex on the Metabolism of Triple-Negative Breast Cancer Tumors of a Xenograft Mouse Model
authors Carneiro, TJ; Araujo, R; Vojtek, M; Goncalves-Monteiro, S; de Carvalho, ALMB; Marques, MPM; Diniz, C; Gil, AM
nationality International
journal INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
author keywords platinum(II); palladium(II); spermine; cisplatin; human triple-negative breast cancer; xenografts; mice; NMR; metabolomics
keywords METABOLOMICS ANALYSIS; DNA-BINDING; TISSUE; CELL; NMR; PALLADIUM(II); CISPLATIN; PROFILES; CHEMOTHERAPY; PLASMA
abstract The interest in palladium(II) compounds as potential new anticancer drugs has increased in recent years, due to their high toxicity and acquired resistance to platinum(II)-derived agents, namely cisplatin. In fact, palladium complexes with biogenic polyamines (e.g., spermine, Pd(2)Spm) have been known to display favorable antineoplastic properties against distinct human breast cancer cell lines. This study describes the in vivo response of triple-negative breast cancer (TNBC) tumors to the Pd(2)Spm complex or to cisplatin (reference drug), compared to tumors in vehicle-treated mice. Both polar and lipophilic extracts of tumors, excised from a MDA-MB-231 cell-derived xenograft mouse model, were characterized through nuclear magnetic resonance (NMR) metabolomics. Interestingly, the results show that polar and lipophilic metabolomes clearly exhibit distinct responses for each drug, with polar metabolites showing a stronger impact of the Pd(II)-complex compared to cisplatin, whereas neither drug was observed to significantly affect tumor lipophilic metabolism. Compared to cisplatin, exposure to Pd(2)Spm triggered a higher number of, and more marked, variations in some amino acids, nucleotides and derivatives, membrane precursors (choline and phosphoethanolamine), dimethylamine, fumarate and guanidine acetate, a signature that may be relatable to the cytotoxicity and/or mechanism of action of the palladium complex. Putative explanatory biochemical hypotheses are advanced on the role of the new Pd(2)Spm complex in TNBC metabolism.
publisher MDPI
isbn 1422-0067
year published 2021
volume 22
issue 19
digital object identifier (doi) 10.3390/ijms221910775
web of science category 16
subject category Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
unique article identifier WOS:000707774400001
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journal analysis (jcr 2019):
journal impact factor 4.556
5 year journal impact factor 4.653
category normalized journal impact factor percentile 74.208
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