Page 67 - SDIR5 Abstract book 21 12 2021.

POSTER PRESENTATIONS

P27

Molecular mechanisms of nanoparticle-mediated biological effects in doxorubicin treated
cells

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3
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1,2
Karmen Stankov , Jasmina Katanić , Bojan Stanimirov , Nebojša Pavlović , Gordana Bogdanović 2
1 Department of Biochemistry, Faculty of Medicine, University of Novi Sad, Novi Sad, Vojvodina, Serbia
2 Academy of medical sciences, Serbian medical society, Serbia
3 Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Novi Sad, Vojvodina, Serbia

Background: Engineered nanomaterials are at the leading edge of the rapidly advancing domain of
nanomedicine, particularly in cancer research. Cytoprotective properties of nanoparticles due to their ROS
scavenging capacity may significantly increase the therapeutic potential of cytotoxic drugs. Therefore, the
main aim of our in vitro study was to investigate the expression of genes in fullerenol (FNM) treated cells
in order to evaluate its therapeutic potential. Material and methods: Expression of genes involved in key
cellular functions and processes, such as proliferation, apoptosis, redox regulation, DNA damage and repair
was measured in K562 cells by the means of quantitative real-time PCR. RNA for cDNA synthesis was
isolated from doxorubicin (DOX) treated erythroleukemia K562 cells, from FNM and from FNM+DOX
treated cells. Gene expression was analyzed using comparative Ct method, and statistical analysis was
performed using one-way Anova and Tuckey’s post-hoc test. Results: Expression analysis of genes involved
in antioxidative cell defense showed that FNM significantly suppresses DOX-induced inhibition of MnSOD,
GR and gGCS. DOX-induced block in proliferation, as shown by decreased Ki67 expression was maintained
also in FNM+DOX group of cells. FMN alone induced down-regulation of pro-apoptotic BAX, which is
mediated by FMN-induced over-expression of BAX-inhibitor. Up-regulated BAX-inhibitor diminishes ER-
stress-induced ROS accumulation and it is involved in induction of HMOX, gGCS and GST in K562 cells.
Expression of hOGG1 coding for base-excision repair enzyme was inhibited in FNM+DOX group, indicating
that fullerenol contributes to increased K562 sensitivity to DOX. Conclusion: Fullerenol modulates redox
status of DOX-treated K562 cells, it synergistically contributes to the proliferation block induced by DOX
and exerts important ROS scavenging and apoptosis-modulating properties in erythroleukemia cells.
Key words: oxidative stress, nanoparticle, doxorubicin, apoptosis.
Acknowledgements: Supported by the Ministry of Education, Science and Technological Development,
Republic of Serbia, Grant III41012, and Project of special interest for sustainable development in the
Autonomous Province of Vojvodina No. 142-451-2283/2021-01/02.

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