PhD Scientific Days 2023

Pharmaceutical Sciences II.

Multiparametric study of peptide-based daunorubicin conjugates for targeted therapy of pancreatic tumour cell line

Előadó neve

Szász, Zsófia, MSc

Neptun code

IKMTJT

Előadó munkahelye

Department of Genetics, Cell- and Immunobiology

Előadó telefonszáma

+3612102930/56232

Előadó e-mail címe

szaszadriennzsofia@gmail.com

Az előadás címe

Multiparametric study of peptide-based daunorubicin conjugates for targeted therapy of pancreatic tumour cell line

Szerző(k) neve és munkahelye

Zsófia Szász, Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest
Kata Nóra Enyedi, Institute of Chemistry, Faculty of Sciences, Eötvös Loránd University, Budapest

Bemutatás módja

Szóbeli

Szekció

Pharmaceutical Sciences II.

Language of the presentation

English

Preferred session

Pharmaceutical Sciences

Összefoglaló szövege

Introduction: Daunorubicin (Dau) is a cytotoxic antitumour agent which side effect profile and pharmacokinetics can be favourably influenced by conjugation with the targeting peptides. The peptide-based conjugates are able to selectively target Dau to tumour cells through binding to and internalisation of receptors overexpressed on the tumour cells. The targeting peptide sequence of the investigated conjugates was originally selected by using a phage library technique on pancreas tumour cells. Peptide conjugates provide a new approach to targeted tumour therapy for pancreas tumours.
Aim: The present study aims to determine the mechanism of action of Dau-peptide conjugates on a pancreatic adenocarcinoma (PANC-1) cell line. For control studies, a mouse cardiomyocyte cell line (HL-1) was used to investigate the cardiotoxic effects of the conjugates.
Methods: Three conjugates (EKK-31, EKK-3, EKK-16), selected by their IC50 values, were investigated by the analysis of the following parameters with the corresponding methods: (i) apoptotic effect – flow cytometry (CytoFLEX) (ii) morphometric changes – holographic microscopy (HoloMonitorM4) and (iii) cardiotoxic effect – luminescence-based viability assay (CellTiter Glo).
Results: After 48 hours, 10 μM EKK-16, similarly to Dau, increased ~2-fold the number of late apoptotic cells compared to the medium control. Moreover, after 72 h treatment with EKK-16, the number of late apoptotic cells was increased 9.5-fold. Cell morphology changes were characterized by monitoring the average cell area, optical thickness and volume over 72 hours. EKK16 significantly increased cell area 1.5 fold and volume 2 fold after 24 hours, but optical thickness was increased 2.5 fold only after 48 hours. These morphometric results suggest that EKK-16 induces senescence in PANC-1 cells in the short term (24 h). In our cardiotoxicity study on HL-1 cells, 100 µM EKK-16 reduced cell viability to 3%, similar to Dau at 10 µM, whereas cardiomyocyte viability was >80% after treatment with all conjugates at 1 and 10 µM.
Conclusion: EKK-16 is a promising Dau-containing peptide conjugate that selectively targets PANC-1 cells. Based on our results, its action is thought to be mediated by cellular senescence (short term) and subsequent apoptotic cell death (long term).
Funding: EFOP-3.6.3-VEKOP-16-2017-00009, ÚNKP-22-3-II-SE-19

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences

Supervisor

Dr. Lajkó Eszter, Prof. Dr. Kőhidai László

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6041

Start

15:30

End

15:45

Authors (legacy)

Zsófia Szász, Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest
Kata Nóra Enyedi, Institute of Chemistry, Faculty of Sciences, Eötvös Loránd University, Budapest