PhD Scientific Days 2025

Poster Session II. - G: Pharmaceutical Sciences and Health Technologies

Effect of Copper Chelating Agents on KRAS Mutant Colorectal SW48 Cell Lines

Előadó neve

Dr. Üveges Elina

Neptun code

GH8E3L

Előadó munkahelye

Semmelweis University Doctoral College Division of Pharmaceutical Sciences and Health Technologies

Előadó telefonszáma

+36305626354

Előadó e-mail címe

uveges.elina@stud.semmelweis.hu

Az előadás címe

Effect of Copper Chelating Agents on KRAS Mutant Colorectal SW48 Cell Lines

Szerző(k) neve és munkahelye

Dr. Elina Üveges¹

1: Semmelweis University Doctoral College Division of Pharmaceutical Sciences and Health Technologies

Bemutatás módja

Poszter

Szekció

Poster Session II. - G: Pharmaceutical Sciences and Health Technologies

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction: Based on earlier studies, certain KRAS mutations have unique capabilities regarding copper transport and metabolism. Exploiting these qualities can be key to developing new therapies for these tumours, as there is no specific treatment in clinical practice for cancers harbouring KRAS mutation.
Aim: Our aim was to compare different KRAS mutations using a colorectal SW48 model, with SW48 wild type, SW48 G12C, SW48 G12D, and SW48 G12V cells. The object of the comparison was the response to different copper chelating agents. Different sensitivity would indicate significant difference of copper metabolism in these cell lines and would confirm our earlier findings.
Method: We used the following four copper chelating agents in our experiments: di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT), neocuproine, di-2-piridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) and ammonium tetrathiomolibdate (TTM). First, we added different concentrations of copper chelators for 72 hours and measured EC50 values with Presto Blue™ cell viability assay. In our second experiment we subjected the different cell lines to a low concentration (10 µM) TTM treatment, and cell numbers were measured every day for 96 hours using an automated cell counter.
Results: EC50 values for neocuproine were 1.0 ± 0.2 µM, 1.6 ± 0.2 µM, 0.8 ± 0.2 µM, 2.6 ± 0.5 µM, for Dp44mT they were 0.03 ± 0.01 µM, 0.07 ± 0.01 µM, 0.02 ± 0.02 µM, 0.06 ± 0.04 µM, for DpC they were 0.01 ± 0.01 µM, 0.52 ± 0.01 µM, 0.02 ± 0.01 µM, 0.08 ± 0.01 µM in SW48 WT, SW48 G12C, SW48 G12D and SW48 G12V cells respectively. Cell growth is slightly repressed as a result of TTM treatment in all three mutant cell lines.
Conclusion: SW48 wild type and SW48 G12D cells have a higher sensitivity to copper chelating agents compared to G12C and G12V cells. This can be a result of the higher bioavailable copper levels in G12C and G12V mutant cells. Based on earlier experiments, SW48 G12D mutant cells are similar to wild type cells in several other aspects, while G12C and G12V cells show different tendencies regarding copper homeostasis. This study shows that altered copper metabolism does not occur in all KRAS mutations, but is highly dependent on the exact point mutation, and these results are consistent with our previous findings.
Funding: This study was supported by the SE250+ Excellence PhD Scholarship

University

Semmelweis University

Supervisor

Dr. Szoboszlai Norbert

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7499

Start

19:18

End

19:24