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Antiproliferative Properties of Scandium Exopolysaccharide Complexes on Several Cancer Cell Lines
Javier Muñoz-Garcia1, Mattia Mazza2,3, Cyrille Alliot2,4
1Institut de Cancérologie de l'Ouest, Université de Nantes, Blvd Jacques Monod, F-44805 Saint-Herblain, France.
Abstract:
Antimetastatic properties on both murine and human osteosarcoma cell lines (POS-1 and KHOS) have been evidenced using exopolysaccharide (EPS) derivatives, produced by Alteromonas infernus bacterium. These derivatives had no significant effect on the cell cycle neither a pro-apoptotic effect on osteosarcoma cells. Based on this observation, these EPSs could be employed as new drug delivery systems for therapeutic uses. A theranostic approach, i.e., combination of a predictive biomarker with a therapeutic agent, has been developed notably by combining with true pair of theranostic radionuclides, such as scandium 47Sc/44Sc. However, it is crucial to ensure that, once complexation is done, the biological properties of the vector remain intact, allowing the molecular tropism of the ligand to recognize its molecular target. It is important to assess if the biological properties of EPS evidenced on osteosarcoma cell lines remain when scandium is complexed to the polymers and can be extended to other cancer cell types. Scandium-EPS complexes were thus tested in vitro on human cell lines: MNNG/HOS osteosarcoma, A375 melanoma, A549 lung adenocarcinoma, U251 glioma, MDA231 breast cancer, and Caco2 colon cancer cells. An xCELLigence Real Cell Time Analysis (RTCA) technology assay was used to monitor for 160 h, the proliferation kinetics of the different cell lines. The tested complexes exhibited an anti-proliferative effect, this effect was more effective compared to EPS alone. This increase of the antiproliferative properties was explained by a change in conformation of EPS complexes due to their polyelectrolyte nature that was induced by complexation. Alterations of both growth factor-receptor signaling, and transmembrane protein interactions could be the principal cause of the antiproliferative effect. These results are very promising and reveal that EPS can be coupled to scandium for improving its biological effects and also suggesting that no major structural modification occurs on the ligand.
Insights
Exopolysaccharide (EPS) derivatives from Alteromonas infernus show antimetastatic properties. When complexed with scandium, these EPS-scandium compounds enhance anti-proliferative effects on various cancer cells, indicating potential as drug delivery systems.
Area of Science:
- Biomaterials Science
- Cancer Biology
- Radiochemistry
Background:
- Exopolysaccharides (EPS) from Alteromonas infernus exhibit antimetastatic properties against osteosarcoma cell lines.
- EPS derivatives did not significantly affect cell cycle or induce apoptosis, suggesting potential as drug delivery vehicles.
- A theranostic approach combining predictive biomarkers with therapeutic agents, such as scandium radionuclides (Sc-47/Sc-44), is under development.
Purpose of the Study:
- To evaluate if the biological properties of EPS remain intact after complexation with scandium.
- To assess the anti-proliferative effects of scandium-EPS complexes on various human cancer cell lines.
- To investigate the potential of EPS-scandium complexes as enhanced therapeutic agents.
Main Methods:
- In vitro testing of scandium-EPS complexes on human osteosarcoma, melanoma, lung adenocarcinoma, glioma, breast cancer, and colon cancer cell lines.
- Real-time cell proliferation monitoring using xCELLigence Real Cell Time Analysis (RTCA) technology over 160 hours.
- Comparative analysis of anti-proliferative effects between EPS alone and scandium-EPS complexes.
Main Results:
- Scandium-EPS complexes demonstrated a significant anti-proliferative effect on tested cancer cell lines.
- The anti-proliferative efficacy of EPS was enhanced upon complexation with scandium.
- Complexation-induced conformational changes in EPS, due to their polyelectrolyte nature, are hypothesized to cause this enhanced effect.
- Potential mechanisms include alterations in growth factor-receptor signaling and transmembrane protein interactions.
Conclusions:
- EPS can be effectively coupled with scandium to improve their biological effects, particularly anti-proliferative activity.
- Scandium-EPS complexes show promise as enhanced therapeutic agents for various cancer types.
- No major structural modifications were observed in the EPS ligand upon scandium complexation, preserving its biological activity.
