PhD Scientific Days 2024

Poster Session E - Molecular Medicine 2.

Pigmentation modulates ferroptosis sensitivity in melanoma

Előadó neve

Ms. Pál, Dorottya

Neptun code

PJDI3L

Előadó munkahelye

Department of Physiology

Előadó telefonszáma

+36707913570

Előadó e-mail címe

pal.dorottya@phd.semmelweis.hu

Az előadás címe

Pigmentation modulates ferroptosis sensitivity in melanoma

Szerző(k) neve és munkahelye

Dorottya Pál^1,2, Alexandra Lakatos^1,2, Anna S. Lengyel, MD¹, Anna S. Lengyel³, Benedek Nagy^1,2, Petra N. Péter^1,3, Anna Ascsillán¹, Botond Szabolcs^1,3, Elmar G. Lutz^1,3, Lajos V. Kemény MD, PhD^1,2,4

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

Bemutatás módja

Poszter

Szekció

Poster Session E - Molecular Medicine 2.

Language of the presentation

Hungarian

Preferred session

Molecular Medicine

Összefoglaló szövege

Introduction:
Given the lack of clinically available approaches to overcome resistance to modern targeted immunotherapies for metastatic melanoma, a better understanding of cell death regulatory pathways is warranted in melanoma.
In melanoma, reactive oxygen species have been demonstrated to play a significant and complex role. It has been shown that promoting lipid ROS-mediated, iron-dependent cell death ferroptosis has promise in dedifferentiated, multi-drug resistant melanoma.
However, it is unknown why dedifferentiated melanoma cells are susceptible to ferroptotic cell death and why differentiated melanoma cells are resistant to ferroptosis.
Aims:
We aimed to investigate the role of pigmentation in modulating ferroptosis cell death in melanoma.
Method:
The tyrosinase activity was modulated by genetic ablation of the tyrosinase gene with CRISPR-Cas9 in mouse B16 melanoma cells. Clones lacking tyrosinase mRNA were used to model tyrosinase deficiency genetically. Certain experiments utilized pharmacologic inhibition of tyrosinase by pre-treating pigmented cells with 200uM of PTU for at least 5 days.
Viability assays have been performed with various compounds inducing ferroptosis. Melanoma cell lines were treated with ferroptosis-inducing compounds at 10 concentrations. Cell viability was measured using the CellTiter-Glo Assay.
For Lipid ROS assay detection, two days after B16 cells were seeded, a fluorescent radio probe, Bodipy C11, was added to each well and incubated. The extent of lipid peroxidation was measured using a Leica fluorescence microscope and quantified with ImageJ.
Glutathione levels were measured according to the manufacturer’s instructions in B16 melanoma cells.
Results:
Our results demonstrate that in melanoma, both pharmacological and genetic inhibition of pigmentation modulated sensitivity to ferroptosis. In line with these observations, we have observed that pigment production alters sensitivity to lipid peroxidation induced by ferroptosis compounds.
Possibly, low glutathione levels in pigmented cells may contribute to increased ferroptosis sensitivity.
Conclusion:
Our results shed light on regulating ferroptosis by pigment production in melanoma cells. However, further studies are required on the mechanism of how pigmentation modulates ferroptosis.
Funding:
HCEMM Grant 2022-27, OTKA KFI Grant 2021-25, Bolyai Scholarship 2021-24

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.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7351

Start

15:05

End

15:08