PhD Scientific Days 2022

Pathology and Oncology II. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Tumor inhibitory mechanism of novel tamoxifen derivates on breast- and pancreatic cancer cell lines

Előadó neve

Kalabay, Márton

Előadó munkahelye

Dept. of Genetics, Cell and Immunobiology

Előadó telefonszáma

+36202942726

Előadó e-mail címe

martonkalabay@gmail.com

Az előadás címe

Tumor inhibitory mechanism of novel tamoxifen derivates on breast- and pancreatic cancer cell lines

Szerző(k) neve és munkahelye

Márton Kalabay1, Zsófia Szász1, Eszter Lajkó1, Orsolya Láng1, László Kőhidai1
1Dept. of Genetics, Cell and Immunobiology, Semmelweis University, Budapest

Bemutatás módja

Poszter

Szekció

Pathology and Oncology II. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Language of the presentation

Hungarian

Preferred session

Pathology and Oncology

Összefoglaló szövege

Introduction: Tamoxifen is a well-known antitumor drug, that modulates several estrogen receptor (ER)-dependent and independent cell physiological pathways. Based on previous research, conjugation of the original compound with ferrocene and halogen groups can significantly improve its cytotoxic effect.
Aims: The main objective of this study is to reveal the mechanism behind the improved antitumor effect of the halogenated (T6) and ferrocene-linked (T5 and T15) tamoxifen derivates. To uncover the means of action (i) the ER expression profile of the model cells is screened, (ii) impact on the cell cycle is measured, (iii) levels of cell cycle regulators are quantified and (iv) structure-activity relationships are described.
Methods: Three cell lines were used: PANC1 (pancreas adenocc.), MCF7 (ER+ breast adenocc.), MDA-MB231 (ER- breast adenocc.). The ER expression profile was described by indirect immunocytochemistry. Impact on the cell cycle was measured by flow cytometry with propidium-iodide staning. Expression of 24 cell cycle regulators were measured by qPCR.
Results: MDA-MB231 and MCF7 cells express the ERα, ERβ, GPER1 and ESRRA isoforms. On PANC1 cells only the ERα and GPER1 were detected in a significant amount. The tamoxifen treatment induces S phase arrest on MCF7 and a G1 phase arrest on MDA-MB231. The ferrocene-linked derivatives arrest the cell cycle in the G1 phase on breast cancer cells, while the halogenated derivative caused a G2/M phase arrest ont he pancreatic cancer cell line. Tamoxifen treatment elevated the expression of CCNA1, CDK6, E2F1 and RB1, while suppressing CCNB1, CCNB2, CCND1 and CCND2. The ferrocene-linked derivatives upregulate CCNA1, CDC25C, CDK4 and E2F1, and lower the expression of CCNE1 and CDC25A. The halogenated derivative results in a higher expression of CCNA1, CCNB1, CCNE1, CDK1, CDK4, E2F1 and RB1.
Conclusion: Our results suggest that the investigated novel tamoxifen derivates are possibly acting through the arrest of the cell cycle. The observed stop in the different phases are strongly in connection with the different ER isoforms expressed by the tumor cells.
Funding: This research was supported by the National Research, Development and Innovation Office (NVKP_16-1-2016-0036), by the Ministry of Innovation and Technology (ÚNKP-21-2-I-SE-35) and by the EFOP-3.6.3-VEKOP-16-2017-00009 project.

University and Doctoral School

Semmelweis University, Doctoral School of Molecular Medicine

Supervisor

Prof. Dr. László Kőhidai

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

6141

Start

11:25

End

11:30

Authors (legacy)

Márton Kalabay1, Zsófia Szász1, Eszter Lajkó1, Orsolya Láng1, László Kőhidai1
1Dept. of Genetics, Cell and Immunobiology, Semmelweis University, Budapest