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Evaluation of the Cytotoxic Effect of Pd2Spm against Prostate Cancer through Vibrational Microspectroscopies
Raquel C Laginha1, Clara B Martins1, Ana L C Brandão1
1Molecular Physical-Chemistry R&D Unit, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal.
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 (Pd2Spm) 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 Pd2Spm 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 Pd2Spm. In turn, the Pd-agent showed a more significant impact on proteins.
Insights
A new palladium-2 spermine complex (Pd2Spm) shows potential as an antineoplastic agent. It selectively targets cancer cells by altering DNA, lipids, and proteins, offering a promising alternative to cisplatin.
Area of Science:
- Biochemistry
- Molecular Biology
- Materials Science
Background:
- Developing selective antineoplastic agents is crucial for cancer therapy.
- Evaluating cytotoxic effects on both healthy and cancerous cells is essential.
- Palladium complexes are investigated for their anticancer properties.
Purpose of the Study:
- To assess the selective antitumoral potential of a novel palladium-2 spermine complex (Pd2Spm).
- To compare the molecular mechanisms of Pd2Spm with cisplatin in prostate cancer cells.
- To identify molecular biomarkers of drug impact using vibrational spectroscopy.
Main Methods:
- Testing Pd2Spm and cisplatin on healthy (PNT-2) and cancer (LNCaP, PC-3) human prostate cell lines.
- Utilizing Fourier Transform Infrared (FTIR) and Raman microspectroscopy to analyze molecular changes.
- Applying Principal Component Analysis (PCA) to vibrational data for metabolic change identification.
Main Results:
- Both drugs induced metabolic changes affecting DNA, lipids, and proteins.
- Pd2Spm and cisplatin altered DNA conformation (B-DNA to Z-DNA or A-DNA).
- Cisplatin showed a greater impact on lipids, while Pd2Spm significantly affected proteins.
Conclusions:
- Pd2Spm demonstrates selective antitumoral potential by impacting cancer cell molecular components.
- Vibrational spectroscopy and PCA are effective tools for elucidating drug mechanisms of action.
- Pd2Spm represents a promising candidate for further development as an antineoplastic agent.
