{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T10:05:17Z","timestamp":1766829917775,"version":"build-2065373602"},"reference-count":93,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/50011\/2020 and UIDP\/50011\/2020, UIDB\/00070\/2020, UIDB\/50006\/2020, PTNMR and partially supported by Infrastructure Project N\u00ba 022161,PTDC\/QEQ-MED\/1890\/2014 , PD\/BD\/135460\/2017 ,SFRH\/BD\/145920\/2019"],"award-info":[{"award-number":["UIDB\/50011\/2020 and UIDP\/50011\/2020, UIDB\/00070\/2020, UIDB\/50006\/2020, PTNMR and partially supported by Infrastructure Project N\u00ba 022161,PTDC\/QEQ-MED\/1890\/2014 , PD\/BD\/135460\/2017 ,SFRH\/BD\/145920\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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, Pd2Spm) 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 Pd2Spm 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 Pd2Spm 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 Pd2Spm complex in TNBC metabolism.<\/jats:p>","DOI":"10.3390\/ijms221910775","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T16:23:58Z","timestamp":1633623838000},"page":"10775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Impact of the Pd2Spm (Spermine) Complex on the Metabolism of Triple-Negative Breast Cancer Tumors of a Xenograft Mouse Model"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4841-7860","authenticated-orcid":false,"given":"Tatiana J.","family":"Carneiro","sequence":"first","affiliation":[{"name":"Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Rita","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9257-7020","authenticated-orcid":false,"given":"Martin","family":"Vojtek","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Drug Sciences, Laboratory of Pharmacology, Faculty of Pharmacy, University of Porto, 4150-755 Porto, Portugal"}]},{"given":"Salom\u00e9","family":"Gon\u00e7alves-Monteiro","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Drug Sciences, Laboratory of Pharmacology, Faculty of Pharmacy, University of Porto, 4150-755 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-3321","authenticated-orcid":false,"given":"Ana L. M. Batista","family":"de Carvalho","sequence":"additional","affiliation":[{"name":"\u201cQu\u00edmica-F\u00edsica Molecular\u201d, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8391-0055","authenticated-orcid":false,"given":"Maria Paula M.","family":"Marques","sequence":"additional","affiliation":[{"name":"\u201cQu\u00edmica-F\u00edsica Molecular\u201d, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"},{"name":"Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, 3000-456 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-9360","authenticated-orcid":false,"given":"Carmen","family":"Diniz","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Drug Sciences, Laboratory of Pharmacology, Faculty of Pharmacy, University of Porto, 4150-755 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-4364","authenticated-orcid":false,"given":"Ana M.","family":"Gil","sequence":"additional","affiliation":[{"name":"Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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