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通过振动微光谱评估 PdSpm 对前列腺癌的细胞毒性作用。

Evaluation of the Cytotoxic Effect of PdSpm against Prostate Cancer through Vibrational Microspectroscopies.

机构信息

Molecular Physical-Chemistry R&D Unit, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal.

Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, 3000-456 Coimbra, Portugal.

出版信息

Int J Mol Sci. 2023 Jan 18;24(3):1888. doi: 10.3390/ijms24031888.

Abstract

Regarding the development of new antineoplastic agents, with a view to assess the selective antitumoral potential which aims at causing irreversible damage to cancer cells while preserving the integrity of their healthy counterparts, it is essential to evaluate the cytotoxic effects in both healthy and malignant human cell lines. In this study, a complex with two Pd(II) centers linked by the biogenic polyamine spermine (PdSpm) was tested on healthy (PNT-2) and cancer (LNCaP and PC-3) prostate human cell lines, using cisplatin as a reference. To understand the mechanisms of action of both cisplatin and PdSpm at a molecular level, Fourier Transform Infrared (FTIR) and Raman microspectroscopies were used. Principal component analysis was applied to the vibrational data, revealing the major metabolic changes caused by each drug, which were found to rely on DNA, lipids, and proteins, acting as biomarkers of drug impact. The main changes were observed between the B-DNA native conformation and either Z-DNA or A-DNA, with a higher effect on lipids having been detected in the presence of cisplatin as compared to PdSpm. In turn, the Pd-agent showed a more significant impact on proteins.

摘要

关于新型抗肿瘤药物的开发,为了评估其选择性抗肿瘤潜力,旨在对癌细胞造成不可逆转的损伤,同时保持其健康对应物的完整性,有必要评估健康和恶性人细胞系中的细胞毒性作用。在这项研究中,使用顺铂作为参比物,对健康(PNT-2)和癌症(LNCaP 和 PC-3)前列腺人细胞系测试了由生物多胺精胺连接的两个 Pd(II)中心的配合物(PdSpm)。为了在分子水平上理解顺铂和 PdSpm 的作用机制,使用了傅里叶变换红外(FTIR)和拉曼微光谱学。对振动数据进行了主成分分析,揭示了每种药物引起的主要代谢变化,这些变化依赖于 DNA、脂质和蛋白质,作为药物影响的生物标志物。主要变化观察到在 B-DNA 天然构象和 Z-DNA 或 A-DNA 之间,与 PdSpm 相比,顺铂存在时检测到脂质的影响更高。反过来,Pd 试剂对蛋白质的影响更显著。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a1a/9916163/765e4ea0f561/ijms-24-01888-g001.jpg

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