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Updated: Jun 27, 2025
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Vibrational microspectroscopy as a tool to unveil new chemotherapeutic strategies against osteosarcoma
Raquel C Laginha1, Jéssica D Silva1, Gianfelice Cinque2
1Molecular Physical-Chemistry R&D Unit, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal.
Abstract:
Over the years, osteosarcoma therapy has had a significative improvement with the use of a multidrug regime strategy, increasing the survival rates from less than 20 % to circa 70 %. Different types of development of new antineoplastic agents are critical to achieve irreversible damage to cancer cells, while preserving the integrity of their healthy counterparts. In the present study, complexes with two and three Pd(II) centres linked by the biogenic polyamines: spermine (Pd2SpmCl4) and spermidine (Pd3Spd2Cl6) were tested against non-malignant (osteoblasts, HOb) and cancer (osteosarcoma, MG-63) human cell lines. Either alone or in combination according to the EURAMOS-1 protocol, they were used versus cisplatin as a drug reference. By evaluating the cytotoxic effects of both therapeutic approaches (single and drug combination) in HOb and MG-63 cell lines, the selective anti-tumoral potential is assessed. To understand the different treatments at a molecular level, Synchrotron Radiation Fourier Transform Infrared and Raman microspectroscopies were applied. Principal component analysis and hierarchical cluster analysis are 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-to-cell impact. The main changes were observed for the B-DNA native conformation to either Z-DNA (higher in the presence of polynuclear complexes) or A-DNA (preferably after cisplatin exposure). Additionally, a higher effect upon variation in proteins content was detected in drug combination when compared to single drug administration proving the efficacy of the EURAMOS-1 protocol with the new drugs tested.
Insights
New palladium (Pd(II)) complexes with polyamines show selective anti-cancer effects against osteosarcoma cells. These novel agents, tested alone or with cisplatin, alter DNA and protein content, demonstrating potential for improved osteosarcoma treatment.
Area of Science:
- Materials Chemistry
- Biomedical Sciences
- Cancer Research
Background:
- Osteosarcoma treatment has improved with multidrug strategies, but new antineoplastic agents are needed for better efficacy and reduced side effects.
- Polynuclear palladium(II) complexes offer a promising avenue for developing novel anti-cancer drugs due to their unique chemical properties.
Purpose of the Study:
- To synthesize and evaluate the anti-tumoral potential of two novel polynuclear palladium(II) complexes, Pd2SpmCl4 and Pd3Spd2Cl6, against human osteosarcoma (MG-63) and non-malignant osteoblast (HOb) cell lines.
- To assess the efficacy of these complexes when used alone or in combination with cisplatin, following the EURAMOS-1 protocol.
- To investigate the molecular mechanisms underlying the cytotoxic effects of these palladium complexes using advanced spectroscopic techniques.
Main Methods:
- Synthesis and characterization of Pd(II) complexes with spermine and spermidine.
- Cytotoxicity assays on human osteosarcoma (MG-63) and osteoblast (HOb) cell lines.
- Treatment protocols included single drug administration and combination therapy (EURAMOS-1 protocol) with cisplatin.
- Synchrotron Radiation Fourier Transform Infrared (SR-FTIR) and Raman microspectroscopy for molecular analysis.
- Chemometric analysis (Principal Component Analysis, Hierarchical Cluster Analysis) of spectroscopic data.
Main Results:
- The Pd(II) complexes exhibited selective cytotoxic effects against MG-63 cells compared to HOb cells.
- Combination therapy, particularly with the polynuclear complexes, showed enhanced efficacy compared to single drug treatments.
- Spectroscopic analysis revealed significant alterations in DNA (B-DNA to Z-DNA or A-DNA transitions) and protein content, serving as biomarkers of drug-induced cellular impact.
- The EURAMOS-1 protocol demonstrated increased efficacy when combined with the novel palladium complexes.
Conclusions:
- The novel polynuclear palladium(II) complexes possess selective anti-osteosarcoma activity.
- These complexes, especially in combination therapy, represent a promising strategy for enhancing osteosarcoma treatment outcomes.
- Molecular changes in DNA and proteins are key indicators of the therapeutic impact of these novel agents.
