Pd2Spermine as an Alternative Therapeutics for Cisplatin-Resistant Triple-Negative Breast Cancer

• Type: Article in International Scientific Journal
• Date: 2024

Authors

Carneiro, TJ (Author) Other; de Carvalho, ALMB (Author) Other; Vojtek, M (Author) Other; Laginha, RC (Author) Other; Marques, MPM (Author) Other; Diniz, C (Author) FFUP; Gil, AM (Author) Other

Journal

Title: Journal of Medicinal Chemistry

Vol. 67

Pages: 6839-6853

ISSN: 0022-2623

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-010-99E

DOI: 10.1021/acs.jmedchem.4c00435

Abstract (EN): Cisplatin (cDDP) resistance is a matter of concern in triple-negative breast cancer therapeutics. We measured the metabolic response of cDDP-sensitive (S) and -resistant (R) MDA-MB-231 cells to Pd(2)Spermine(Spm) (a possible alternative to cDDP) compared to cDDP to investigate (i) intrinsic response/resistance mechanisms and (ii) the potential cytotoxic role of Pd(2)Spm. Cell extracts were analyzed by untargeted nuclear magnetic resonance metabolomics, and cell media were analyzed for particular metabolites. CDDP-exposed S cells experienced enhanced antioxidant protection and small deviations in the tricarboxylic acid cycle (TCA), pyrimidine metabolism, and lipid oxidation (proposed cytotoxicity signature). R cells responded more strongly to cDDP, suggesting a resistance signature of activated TCA cycle, altered AMP/ADP/ATP and adenine/uracil fingerprints, and phospholipid biosynthesis (without significant antioxidant protection). Pd(2)Spm impacted more markedly on R/S cell metabolisms, inducing similarities to cDDP/S cells (probably reflecting high cytotoxicity) and strong additional effects indicative of amino acid depletion, membrane degradation, energy/nucleotide adaptations, and a possible beneficial intracellular gamma-aminobutyrate/glutathione-mediated antioxidant mechanism.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15