PhD Scientific Days 2026

Poster Session 2.B - Molecular Medicine

Investigation of the Mechanism of Ferroptosis in Melanoma

Előadó neve

Pál, Dorottya

Neptune code

PJDI3L

Előadó munkahelye

Department of Physiology

Előadó telefonszáma

+36707913570

Előadó e-mail címe

pal.dorottya@phd.semmelweis.hu

Az előadás címe

Investigation of the Mechanism of Ferroptosis in Melanoma

Szerző(k) neve és munkahelye

Dorottya Pál^1,2, Alexandra Lakatos^1,2, Benedek Nagy^1,2, Szabolcs Botond^1,2,3, Marianna Nagy-Schwendtner¹, Katalin Buday PhD^1,2, Lajos Vince Kemény MD, PhD^1,2,3

1: HCEMM-SU Translational Dermatology Research Group, Semmelweis University
2: Department of Physiology, Semmelweis University
3: Department of Dermatology, Venerology and Dermatooncology, Semmelweis University

Bemutatás módja

Poszter

Szekció

Poster Session 2.B - Molecular Medicine

Language of the presentation

Hungarian

Preferred session

Molecular Medicine

Összefoglaló szövege

Introduction
Melanoma is a malignant tumor originating from melanocytes, the pigment producing cells of the skin. Due to limited treatments overcoming resistance to targeted immunotherapies in metastatic melanoma, understanding cell death pathways is crucial. In melanoma, reactive oxygen species have been demonstrated to play a significant and complex role. Ferroptosis is an iron dependent form of cell death mediated by lipid peroxidation, and it is potential therapeutic role has been proposed in melanoma. However the molecular mechanism between pigmentation and ferroptosis remains unknown.
Aims
We aimed to investigate the role of pigmentation in modulating ferroptosis cell death in melanoma.
Methods
The activity of tyrosinase was modulated by CRISPR-Cas9 mediated gene knockout in mouse B16 and human MEL202 melanoma cells (TYR WT), generating tyrosinase deficient models (TYR KO). In some experiments, tyrosinase was pharmacologically inhibited using 200 μM PTU pretreatment for at least five days. Cell viability was assessed after treatment with ferroptosis inducing compounds (ML210, RSL3) at ten concentrations using the CellTiter-Glo assay and we used GraphPad Prism 10.6 software for statistical analysis. Lipid ROS was detected following 3 μM RSL3 treatment using Bodipy C11 staining and fluorescence microscopy, with quantification in ImageJ. GSH levels were measured using Glutathione assay kits in human and mouse melanoma cells, while GPX4 expression was analyzed at both mRNA and protein levels by qPCR and Western blot.
Results
Our results indicate that in melanoma, pharmacological and genetic inhibition of pigmentation affects sensitivity to ferroptosis. Consistent with these findings, we discovered that pigment production influences sensitivity to lipid peroxidation caused by ferroptosis compounds. Reduced levels of GSH and GPX4 in pigmented cells may lead to heightened sensitivity to ferroptosis.
Conclusion
Our results shed light on regulating ferroptosis through pigment production in melanoma cells. The reduced levels of GSH and GPX4 during pigmentation may be responsible for the development of increased sensitivity to ferroptosis. However further studies are needed to understand the mechanism by which pigmentation modulates ferroptosis.
Funding
HCEMM Grant 2022-27, Lendület “Momentum” Grant (LP2024-12/2024)

University

Semmelweis University

Supervisor

Lajos Vince Kemény MD, PhD

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

7351

Start

18:00

End

18:03