EFFECT OF STATINS ON HUMAN NEURAL CELLS

EFFECT OF STATINS ON HUMAN NEURAL CELLS

Celkové hodnotenie

Vedecká práca
93%
Prevedenie (dizajn)
94%
Diskusná interakcia
93%
PoužívateľVedecká prácaDizajnDiskusná interakcia
Mgr. Nikolett Nemcová100%100%80%
Mgr. Jozef Mažerik100%100%100%
Mgr. Martina Knoško Brožová100%100%100%
Mgr. Jaroslava Gužiková100%100%100%
Mgr. Ľuboš Hudák100%100%100%
Mgr. Henrieta Škovierová PhD.100%100%100%
Ing. Katarína Lešková Majdová100%100%100%
Mgr. Bibiána Baďurová100%100%100%
Mgr. Eveline Órásová100%100%100%
RNDr. Monika Švecová100%100%100%
Ing. Zuzana Brnoliaková PhD.80%100%100%
Mgr. Mária Bencúrová100%100%100%
Mgr. Kristián Slíž100%100%100%
RNDr. Romana Záhumenská PhD.100%100%100%
ISBN: 978-80-974608-0-8

EFFECT OF STATINS ON HUMAN NEURAL CELLS

Veronika Kucháriková1 , Tereza Pavlišová2 , Romana Záhumenská , Ján Strnádel , Henrieta Škovierová , Erika Halašová ,
1 Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Medical Biochemistry
2 Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Biomedical Centre Martin
kucharikova14@uniba.sk

Statins are currently the most frequently prescribed drugs for cardiovascular diseases. The effects of statins are related to the inhibition of the conversion of β-hydroxy-β-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate. This effect ensure the inhibition of production of sterols, especially cholesterol, which is part of cell membranes. The result of this process can be a decrease in membrane integrity, which can be useful also in destruction of cancer cells. Another significant effect of statins is the inhibition of isoprenylation of key oncoproteins involved in proliferation and cell cycle [1]. Other pleiotropic effects of statins include suppression of growth, survival, migration and metastasis of tumor cells, angiogenesis, inflammation, but also support of cell death – apoptosis [2]. Glioblastoma is one of the most malignant types of brain tumors, which is associated with high mortality. The median overall survival of patients with glioblastoma is very low, with survival time from the onset of the disease being approximately 15 months after surgical resection of the tumor, radiotherapy or chemotherapy. Recent research has shown the positive effect of statins in the treatment of various cancer diseases such as hepatocellular carcinoma, lung cancer, colorectal cancer and prostate cancer. Nowadays scientific knowledge about the effect of statins on brain tumor and healthy cells is insufficient or diverse. Therefore, we want to contribute to clarifying the molecular mechanisms induced by the presence of statins in tumor brain tissue and point out the possible adjuvant effect of statins during brain cancer treatment. In our project, we focused on the comparison of simvastatin impact on healthy astrocyte and cancer glioblastoma cells. We monitored the confluence and the morphology of cells in the presence of simvastatin. We also studied the simvastatin effect on the cell viability in time and concentration dependent manner. Moreover, we prepared the 3D spheroids from glioblastoma cells to analyze the cellular processes more complex. We foundout that simvastatin had supportive effect on healthy cells at very low concentration, but strong inhibitive impact on cell viability at higher concentration. Healthy cells are much more sensitive to increased concentration of simvastatin compared to cancer cells.

Poďakovanie: 

This work was supported by GUK 234/2023 and APVV-22-0332.

Zdroje: 

[1] Pisanti S, Picardi P, Ciaglia E, D’Alessandro A, Bifulco M (2014): Novel prospects of statins as therapeutic agents in cancer. Pharmacol. Res. 88, 84–98.

[2] Vallianou NG, Kostantinou A, Kougias M, Kazazis C (2014): Statins and cancer. Anticancer Agents Med. Chem. 14(5),706-12.

Diskusia

Hello,

In your poster (Materials and Methods), you mentioned about the cultivation of glioblastoma. May I know how are you cultivating?.

Thank you.

Hello, thank you for your question.

In presented project we used a commercially available cell line T98G (ECACC). We followed the conditions which are routinely used and have been published in our articles. T98G cells were grown in DMEM medium supplemented with 10% fetal bovine serum, 100 I.U./ ml of penicillin and 0.1 mg/ml streptomycin at an optimal cell density of 1 x 105 cells/cm2, 37 °C and 5 % CO2 in humidified atmosphere.

Good morning, congratulations to your results. I am curious if you plan this type of experiments on other statins as well, not only simvastatin (lipophilic type) but on hydrophilic type as well. Thanks in advance for your consideration, ZB  

Good morning,

Thank you for your comment. As you mention, there are two types of statins - lipophilic and hydrophilic. In our project we have planned a compheresive study of all eight currently commercially available statins (atorvastatin, cerivastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin). In next steps, we will apply our obtained results on primary glioblastoma culture generated from patients. We would like to focus on the complex screening of all statins at one time/ condition/ experiment and specify the personalised treatment of oncological diseases which could be done by statin sensitization.

Thank you very much for your careful reply. The projectś set-up, as you have described above, seems to be very ambitious. Thus, I cross my fingers for you, all the best from ZB.