The cytotoxic effects of PdCl2 and RuCl3 on the human fibrosarcoma cell line HT1080
Location
Suwanee, PA
Start Date
11-5-2023 1:00 PM
End Date
11-5-2023 4:00 PM
Description
Introduction: Some cancer treatments utilize transitional metals to attack proliferating cancer cells through unique mechanisms. For example, one of the most widely known and used cancer drugs, Cisplatin, creates DNA adducts by binding to DNA bases that consequently prevents DNA repair and leads to apoptosis of these cancer cells. Even though platinum anticancer agents are one of the mainstays for cancer pharmaceuticals, there are other transition metals that are being utilized for anti-cancer treatment, such as osmium, copper, gold, etc. Using this knowledge, in order to expand the utility of transition metals for anticancer treatment we investigated the effects of Ruthenium chloride (RuCl3) and Palladium chloride (PdCl2). A protocol was developed for measuring the effects of RuCl3 and PdCl2 directly on cultured HT1080 cells (a fibrosarcoma cell line) as a prelude to testing the effects of a targeted delivery system. Previous research shows that period five transition metals (ruthenium (Ru), palladium (Pd), etc.) have a significant cytotoxic effect on certain cancer cells. Using these cytotoxic assays, we observed that RuCl3 and PdCl2 have a toxic effect on HT-1080 cells to consistently decrease cell viability past certain concentrations of each transition metal. This study can be used to expand the utility of the unique electrochemical and cytotoxic properties of transition metals to further cancer therapeutics.
Methods: Cultured HT-1080 cells were treated with serially diluted metal cytotoxic agents in each of the 24-well plates containing the tumor cells to conduct our cell viability tests. We performed cytotoxic incubation for 24 hours (RuCl3 sample) and 72 hours (PdCl2). After letting the cells and the metal cytotoxic agents incubate, PrestoBlue was used to determine cell viability/survivability via the Gen5 microplate absorbance reader.
Results: The cytotoxicity assay for RuCl3 yielded the least cell survival with the 1000 uM concentration but no statistically significant difference in the other concentrations. Both trials of PdCl2 yielded the least cell survival with the 500 and 1000 uM concentrations, but no statistically significant difference in the other concentrations. The UV-Vis spectra graphs of water (control graph), and Palladium (both trials) confirmed the chemical structure of each prior to conducting the experiment.
Discussion:
- RuCl3 and PdCl2 have cytotoxic effects on HT-1080 cells.
- Potential problems:
- In vivo, these metals might not be delivered as efficaciously to the cancer cells compared to our experiment where they were delivered directly in solution.
- The potential mechanism of these metals might be similar to Cisplatin which will prevent DNA repair and result in apoptosis in cancer cells. However, it is possible these metals have the potential to be more stable in their delivery and less toxic due to their different chemistries compared to platinum.
Embargo Period
5-31-2023
The cytotoxic effects of PdCl2 and RuCl3 on the human fibrosarcoma cell line HT1080
Suwanee, PA
Introduction: Some cancer treatments utilize transitional metals to attack proliferating cancer cells through unique mechanisms. For example, one of the most widely known and used cancer drugs, Cisplatin, creates DNA adducts by binding to DNA bases that consequently prevents DNA repair and leads to apoptosis of these cancer cells. Even though platinum anticancer agents are one of the mainstays for cancer pharmaceuticals, there are other transition metals that are being utilized for anti-cancer treatment, such as osmium, copper, gold, etc. Using this knowledge, in order to expand the utility of transition metals for anticancer treatment we investigated the effects of Ruthenium chloride (RuCl3) and Palladium chloride (PdCl2). A protocol was developed for measuring the effects of RuCl3 and PdCl2 directly on cultured HT1080 cells (a fibrosarcoma cell line) as a prelude to testing the effects of a targeted delivery system. Previous research shows that period five transition metals (ruthenium (Ru), palladium (Pd), etc.) have a significant cytotoxic effect on certain cancer cells. Using these cytotoxic assays, we observed that RuCl3 and PdCl2 have a toxic effect on HT-1080 cells to consistently decrease cell viability past certain concentrations of each transition metal. This study can be used to expand the utility of the unique electrochemical and cytotoxic properties of transition metals to further cancer therapeutics.
Methods: Cultured HT-1080 cells were treated with serially diluted metal cytotoxic agents in each of the 24-well plates containing the tumor cells to conduct our cell viability tests. We performed cytotoxic incubation for 24 hours (RuCl3 sample) and 72 hours (PdCl2). After letting the cells and the metal cytotoxic agents incubate, PrestoBlue was used to determine cell viability/survivability via the Gen5 microplate absorbance reader.
Results: The cytotoxicity assay for RuCl3 yielded the least cell survival with the 1000 uM concentration but no statistically significant difference in the other concentrations. Both trials of PdCl2 yielded the least cell survival with the 500 and 1000 uM concentrations, but no statistically significant difference in the other concentrations. The UV-Vis spectra graphs of water (control graph), and Palladium (both trials) confirmed the chemical structure of each prior to conducting the experiment.
Discussion:
- RuCl3 and PdCl2 have cytotoxic effects on HT-1080 cells.
- Potential problems:
- In vivo, these metals might not be delivered as efficaciously to the cancer cells compared to our experiment where they were delivered directly in solution.
- The potential mechanism of these metals might be similar to Cisplatin which will prevent DNA repair and result in apoptosis in cancer cells. However, it is possible these metals have the potential to be more stable in their delivery and less toxic due to their different chemistries compared to platinum.