Clara B. Martins, Ana L. M. Batista de Carvalho*, Maria M. Félix, Martin Vojtek, Carmen Diniz, Luís A. E. Batista de Carvalho and Maria P. M. Marques,
{"title":"对顺铂敏感和耐药的间充质三阴性乳腺癌的新化疗方法:振动显微光谱法评估细胞反应。","authors":"Clara B. Martins, Ana L. M. Batista de Carvalho*, Maria M. Félix, Martin Vojtek, Carmen Diniz, Luís A. E. Batista de Carvalho and Maria P. M. Marques, ","doi":"10.1021/acs.analchem.5c02233","DOIUrl":null,"url":null,"abstract":"<p >Triple-negative breast cancer (TNBC) is the most aggressive type of breast tumor with the worst prognosis. New chemotherapeutic agents against TNBC are essential, aiming at a higher efficacy regarding cell growth inhibition and decreased angiogenesis and invasiveness coupled to lower acquired resistance and deleterious side effects. In this study, Raman and Fourier Transform Infrared (FTIR) microspectroscopies were applied to assess the impact of a trinuclear palladium-spermidine complex on human healthy and mesenchymal TNBC cells, with the results being compared to the clinically used drug cisplatin. To understand the metabolic impact of the drugs at the molecular level and identify the main biomarkers, unsupervised multivariate analysis of the data (Principal Component Analysis and Hierarchical Cluster Analysis) was applied to the vibrational data. The results revealed that the new palladium (Pd) agent had a higher effect on the cellular lipids relative to the platinum (Pt) compound (cisplatin), while the latter showed a stronger impact on the proteins. Besides lipids, Pd-agent showed a higher impact in conformational changes from the B-DNA native conformation to either Z- or A-DNA. This suggests the occurrence of distinct pathways of cytotoxicity for these metal complexes. Also, when comparing cisplatin-sensitive to cisplatin-resistant cells, Pd-agent had a more significant impact on νOPO<sub>backbone</sub> from DNA, δCH<sub>2</sub> from lipids and ν<sub>s</sub>CC<sub>ring</sub> from phenylalanine of cisplatin-sensitive cells, while in cisplatin-resistant cells, proteins were the most affected cell components. These results provided spectral features specific to malignancy that led to discrimination between drug-treated and untreated cells. This knowledge is essential for the rational design of improved drugs with a higher efficiency coupled to lower toxicity.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"97 27","pages":"14709–14721"},"PeriodicalIF":6.7000,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"New Chemotherapeutic Approaches to Treatment of Mesenchymal Triple-Negative Breast Cancer-Sensitive and Resistant to Cisplatin: Assessment of Cellular Response by Vibrational Microspectroscopy\",\"authors\":\"Clara B. Martins, Ana L. M. Batista de Carvalho*, Maria M. Félix, Martin Vojtek, Carmen Diniz, Luís A. E. Batista de Carvalho and Maria P. M. Marques, \",\"doi\":\"10.1021/acs.analchem.5c02233\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Triple-negative breast cancer (TNBC) is the most aggressive type of breast tumor with the worst prognosis. New chemotherapeutic agents against TNBC are essential, aiming at a higher efficacy regarding cell growth inhibition and decreased angiogenesis and invasiveness coupled to lower acquired resistance and deleterious side effects. In this study, Raman and Fourier Transform Infrared (FTIR) microspectroscopies were applied to assess the impact of a trinuclear palladium-spermidine complex on human healthy and mesenchymal TNBC cells, with the results being compared to the clinically used drug cisplatin. To understand the metabolic impact of the drugs at the molecular level and identify the main biomarkers, unsupervised multivariate analysis of the data (Principal Component Analysis and Hierarchical Cluster Analysis) was applied to the vibrational data. The results revealed that the new palladium (Pd) agent had a higher effect on the cellular lipids relative to the platinum (Pt) compound (cisplatin), while the latter showed a stronger impact on the proteins. Besides lipids, Pd-agent showed a higher impact in conformational changes from the B-DNA native conformation to either Z- or A-DNA. This suggests the occurrence of distinct pathways of cytotoxicity for these metal complexes. Also, when comparing cisplatin-sensitive to cisplatin-resistant cells, Pd-agent had a more significant impact on νOPO<sub>backbone</sub> from DNA, δCH<sub>2</sub> from lipids and ν<sub>s</sub>CC<sub>ring</sub> from phenylalanine of cisplatin-sensitive cells, while in cisplatin-resistant cells, proteins were the most affected cell components. These results provided spectral features specific to malignancy that led to discrimination between drug-treated and untreated cells. This knowledge is essential for the rational design of improved drugs with a higher efficiency coupled to lower toxicity.</p>\",\"PeriodicalId\":27,\"journal\":{\"name\":\"Analytical Chemistry\",\"volume\":\"97 27\",\"pages\":\"14709–14721\"},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2025-07-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Analytical Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.analchem.5c02233\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ANALYTICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Analytical Chemistry","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.analchem.5c02233","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
New Chemotherapeutic Approaches to Treatment of Mesenchymal Triple-Negative Breast Cancer-Sensitive and Resistant to Cisplatin: Assessment of Cellular Response by Vibrational Microspectroscopy
Triple-negative breast cancer (TNBC) is the most aggressive type of breast tumor with the worst prognosis. New chemotherapeutic agents against TNBC are essential, aiming at a higher efficacy regarding cell growth inhibition and decreased angiogenesis and invasiveness coupled to lower acquired resistance and deleterious side effects. In this study, Raman and Fourier Transform Infrared (FTIR) microspectroscopies were applied to assess the impact of a trinuclear palladium-spermidine complex on human healthy and mesenchymal TNBC cells, with the results being compared to the clinically used drug cisplatin. To understand the metabolic impact of the drugs at the molecular level and identify the main biomarkers, unsupervised multivariate analysis of the data (Principal Component Analysis and Hierarchical Cluster Analysis) was applied to the vibrational data. The results revealed that the new palladium (Pd) agent had a higher effect on the cellular lipids relative to the platinum (Pt) compound (cisplatin), while the latter showed a stronger impact on the proteins. Besides lipids, Pd-agent showed a higher impact in conformational changes from the B-DNA native conformation to either Z- or A-DNA. This suggests the occurrence of distinct pathways of cytotoxicity for these metal complexes. Also, when comparing cisplatin-sensitive to cisplatin-resistant cells, Pd-agent had a more significant impact on νOPObackbone from DNA, δCH2 from lipids and νsCCring from phenylalanine of cisplatin-sensitive cells, while in cisplatin-resistant cells, proteins were the most affected cell components. These results provided spectral features specific to malignancy that led to discrimination between drug-treated and untreated cells. This knowledge is essential for the rational design of improved drugs with a higher efficiency coupled to lower toxicity.
期刊介绍:
Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.