PhD Scientific Days 2021

PO_I_P: Pathology and Oncology I. Posters

Autophagy-induction Derived Non-apoptotic Cell Death in Human Breast Cancer Cell Lines

Előadó neve

Ms. Dankó, Titanilla

Előadó munkahelye

1st Department of Pathology and Experimental Cancer Research, Semmelweis University

Előadó telefonszáma

06302906641

Előadó e-mail címe

tita.danko@gmail.com

Az előadás címe

Autophagy-induction Derived Non-apoptotic Cell Death in Human Breast Cancer Cell Lines

Szerző(k) neve és munkahelye

Titanilla Dankó1, Gábor Petővári1, Dániel Sztankovics1, Dorottya Moldvai1, Regina Raffay1, Patrícia Kóczán1, Péter Lőrincz2, Tamás Visnovitz3, Viktória Zsiros4, Gábor Barna1, Ágnes Márk1, Ildikó Krencz1, Anna Sebestyén1

1 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Üllői út 26. Hungary
2 Department of Anatomy, Cell and Developmental Biology, Eotvos Lorand University, H-1117, Budapest Pázmány Péter sétány 1/c. Hungary
3 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, H-1089, Nagyvárad tér 4. Hungary
4 Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, H-1094, Tűzoltó utca 58. Hungary

Bemutatás módja

Poszter

Szekció

Pathology and Oncology I. Posters

Language of the presentation

Hungarian

Preferred session

Pathology and Oncology

Összefoglaló szövege

Introduction
Metabolic remodeling is a characteristic of cancer cells as a response to treatments. Besides promoting cell growth and survival, the activation of mTOR pathway can also lead to developing resistance mechanism or metastasis formation. In addition, autophagy has a double-edged role as it can either maintain cellular homeostasis or stimulate tumorigenesis in stress.
Aims
As doxycycline (antibiotic agent) has an off-target effect on mitochondrial processes, we aimed to study whether its combination with rapamycin (mTOR inhibitor) is potentially more effective in treatments.
Methods
Rapamycin + doxycycline was tested in several cell lines in vitro, and the mechanism of action was examined using human breast cancer models. Alamar blue and sulforhodamine B tests were applied and the impact of long-term mono- and combination treatments on cell and tumor growth was also monitored in in vitro and in vivo. The induced cell death was detected by flow cytometry and caspase-3 activity measurements. mTOR-, autophagy-, and necroptosis-related proteins were analyzed by WES, Western blot and IHC. Treatment-induced morphological alterations were examined by fluoresce and transmission electron microscopy.
Results
Rapamycin + doxycycline combination could decrease the cell proliferation capacity in the majority of the investigated cell lines in vitro. Continuous rapamycin + doxycycline addition could reduce cell and tumor growth significantly. The studied combination did not cause apoptosis, necrosis or necroptosis, but altered the expressions of LC3 and p62 which were associated with autophagy induction. Lowered intensity of MitoTracker and TOM20 staining suggested that mitophagy could be induced after rapamycin + doxycycline treatment. In parallel, rapamycin + doxycycline combination increased the sign of autophagy (mitophagy)-related alterations at tissue level.
Conclusion
A novel therapeutic strategy could be to co-target mitochondria and mTOR pathway to influence metabolic rewiring and inhibit metabolic adaptation in tumor cells.
Funding
NKFI-FK-128404, National Bionics program-ED_17-1-2017-0009, STIA-KFI2020, VEKOP-2.3.2-16-2016-00002, OTKA120237, PPD-222/2018

University and Doctoral School

Semmelweis University, Doctoral School of Pathological Sciences

Supervisor

Anna Sebestyén, PhD

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

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

3611

Start

11:28

End

11:31

Authors (legacy)

Titanilla Dankó1, Gábor Petővári1, Dániel Sztankovics1, Dorottya Moldvai1, Regina Raffay1, Patrícia Kóczán1, Péter Lőrincz2, Tamás Visnovitz3, Viktória Zsiros4, Gábor Barna1, Ágnes Márk1, Ildikó Krencz1, Anna Sebestyén1

1 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Üllői út 26. Hungary
2 Department of Anatomy, Cell and Developmental Biology, Eotvos Lorand University, H-1117, Budapest Pázmány Péter sétány 1/c. Hungary
3 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, H-1089, Nagyvárad tér 4. Hungary
4 Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, H-1094, Tűzoltó utca 58. Hungary