Studying signal transduction pathways and epigenetic mechanisms that control human SOX genes expression: further insight into their roles in cell fate determination and differentiation

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Studying signal transduction pathways and epigenetic mechanisms that control human SOX genes expression: further insight into their roles in cell fate determination and differentiation (en)
Проучавање сигналних путева и епигенетичких механизама укључених у контролу експресије хуманих SOX гена: даље расветљавање њихове улоге у одређивању судбине и диференцијацији ћелија (sr)
Proučavanje signalnih puteva i epigenetičkih mehanizama uključenih u kontrolu ekspresije humanih SOX gena: dalje rasvetljavanje njihove uloge u određivanju sudbine i diferencijaciji ćelija (sr_RS)
Authors

Publications

Comparative study of antiproliferative potential of three different plant species

Drakulić, Danijela; Stojković, Dejan; Soković, Marina; Stevanović, Milena

(Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade, 2019)

TY  - CONF
AU  - Drakulić, Danijela
AU  - Stojković, Dejan
AU  - Soković, Marina
AU  - Stevanović, Milena
PY  - 2019
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4370
AB  - Cancer represents a heterogeneous group of diseases characterized by uncontrolled 
proliferation of cells, tissue invasion and metastasis. Despite current therapeutic 
strategies which include a combination of surgery, radiation and chemotherapy, cancer 
is second leading cause of death worldwide next to cardiovascular diseases. Therefore, 
the identification of new drugs with high sensitivity to cancer cells is warranted. The 
anticancer properties of plants and their compounds have been shown since ancient 
times and nowadays, there is a growing interest for identification of new plant-derived 
anticancer agents. 
This study was designed to analyze antiproliferative potential of three different plant 
species, namely Ononis spinosa L. (Fabaceae), Anthriscus cerefolium (L.) Hoffm. (Apiaceae) 
and Phlomis fruticosa L. (Lamiaceae). The aerial parts of plants were collected, dried 
and the plant material was subjected to successive extraction with methanol and 
then evaporated to dryness on a rotary vacuum evaporator. The obtained methanolic 
extracts were used for further analysis. Cytotoxic effect of methanolic extracts on HaCaT 
(spontaneously immortalized human keratinocyte cell line), MCF-7 (breast cancer cell 
line), SiHa (cervical cancer cell line), A172 (glioblastoma cell line) and HepG2 (human 
hepatocellular carcinoma cell line) cells was determined by crystal violet colorimetric 
assay. Antiproliferative activity of methanolic extracts on glioblastoma cells was 
evaluated by Ki67 immunostaining.
The results showed that plant extracts reduced viability of all tested cell lines. The 
most active extract was the one from O. spinosa, indicating by the lowest IC50 value. 
Ki67 immunostaining indicates antiproliferative activity of methanolic extracts on 
glioblastoma cells.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade
C3  - The 2nd Balkans-China Mini-symposium on Natural Products and Drug Discovery; 2019 Apr 11-13; Belgrade, Serbia
T1  - Comparative study of antiproliferative potential of three  different plant species
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4370
ER  - 
@conference{
author = "Drakulić, Danijela and Stojković, Dejan and Soković, Marina and Stevanović, Milena",
year = "2019",
abstract = "Cancer represents a heterogeneous group of diseases characterized by uncontrolled 
proliferation of cells, tissue invasion and metastasis. Despite current therapeutic 
strategies which include a combination of surgery, radiation and chemotherapy, cancer 
is second leading cause of death worldwide next to cardiovascular diseases. Therefore, 
the identification of new drugs with high sensitivity to cancer cells is warranted. The 
anticancer properties of plants and their compounds have been shown since ancient 
times and nowadays, there is a growing interest for identification of new plant-derived 
anticancer agents. 
This study was designed to analyze antiproliferative potential of three different plant 
species, namely Ononis spinosa L. (Fabaceae), Anthriscus cerefolium (L.) Hoffm. (Apiaceae) 
and Phlomis fruticosa L. (Lamiaceae). The aerial parts of plants were collected, dried 
and the plant material was subjected to successive extraction with methanol and 
then evaporated to dryness on a rotary vacuum evaporator. The obtained methanolic 
extracts were used for further analysis. Cytotoxic effect of methanolic extracts on HaCaT 
(spontaneously immortalized human keratinocyte cell line), MCF-7 (breast cancer cell 
line), SiHa (cervical cancer cell line), A172 (glioblastoma cell line) and HepG2 (human 
hepatocellular carcinoma cell line) cells was determined by crystal violet colorimetric 
assay. Antiproliferative activity of methanolic extracts on glioblastoma cells was 
evaluated by Ki67 immunostaining.
The results showed that plant extracts reduced viability of all tested cell lines. The 
most active extract was the one from O. spinosa, indicating by the lowest IC50 value. 
Ki67 immunostaining indicates antiproliferative activity of methanolic extracts on 
glioblastoma cells.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade",
journal = "The 2nd Balkans-China Mini-symposium on Natural Products and Drug Discovery; 2019 Apr 11-13; Belgrade, Serbia",
title = "Comparative study of antiproliferative potential of three  different plant species",
pages = "38",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4370"
}
Drakulić, D., Stojković, D., Soković, M.,& Stevanović, M.. (2019). Comparative study of antiproliferative potential of three  different plant species. in The 2nd Balkans-China Mini-symposium on Natural Products and Drug Discovery; 2019 Apr 11-13; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković", University of Belgrade., 38.
https://hdl.handle.net/21.15107/rcub_ibiss_4370
Drakulić D, Stojković D, Soković M, Stevanović M. Comparative study of antiproliferative potential of three  different plant species. in The 2nd Balkans-China Mini-symposium on Natural Products and Drug Discovery; 2019 Apr 11-13; Belgrade, Serbia. 2019;:38.
https://hdl.handle.net/21.15107/rcub_ibiss_4370 .
Drakulić, Danijela, Stojković, Dejan, Soković, Marina, Stevanović, Milena, "Comparative study of antiproliferative potential of three  different plant species" in The 2nd Balkans-China Mini-symposium on Natural Products and Drug Discovery; 2019 Apr 11-13; Belgrade, Serbia (2019):38,
https://hdl.handle.net/21.15107/rcub_ibiss_4370 .

Pyrimethanil: Between efficient fungicide against Aspergillus rot on cherry tomato and cytotoxic agent on human cell lines

Aleksić, Milena; Stanisavljević, Danijela; Ivanov, Marija; Vasiljević, Perica; Stevanović, Milena; Soković, Marina; Stojković, Dejan

(2019)

TY  - JOUR
AU  - Aleksić, Milena
AU  - Stanisavljević, Danijela
AU  - Ivanov, Marija
AU  - Vasiljević, Perica
AU  - Stevanović, Milena
AU  - Soković, Marina
AU  - Stojković, Dejan
PY  - 2019
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1111/aab.12532
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3444
AB  - Pyrimethanil, a synthetic fungicide widely used for the treatment of pre‐ and postharvest fungal diseases on different agricultural crops, was explored for its antifungal activity on different fungal strains. The effect of pyrimethanil on fungal ergosterol was tested by using Aspergillus niger as a model organism. Furthermore, it was investigated, if pyrimethanil can effectively reduce the appearance of Aspergillus rot in wounded cherry tomato fruits. The fungicide cytotoxic effect on different human cell lines was evaluated. In addition, its influence on cell proliferation was studied. A. niger was the most resistant fungal strain (MFC 1.88 μg μL−1) to the effect of pyrimethanil. Addition of ergosterol doubled the MFC on A. niger, indicating that the compound might interfere with ergosterol, main sterol of fungal cell membrane. Disease incidence of A. niger in wounded cherry tomato fruits was not detected with pyrimethanil treatment of 0.75 mg/wound. Some cytotoxic effects of pyrimethanil on human cell lines were recorded already at 50 ng μL−1, while the expression of Ki67 marker of proliferation was decreased with 150 ng μL−1. These results altogether indicate that pyrimethanil is effective in reducing various fungal pathogens, but further use of this fungicide should be reevaluated because of its cytotoxicity.
T2  - Annals of Applied Biology
T1  - Pyrimethanil: Between efficient fungicide against Aspergillus rot on cherry tomato and cytotoxic agent on human cell lines
IS  - 2
VL  - 175
DO  - 10.1111/aab.12532
SP  - 228
EP  - 235
ER  - 
@article{
author = "Aleksić, Milena and Stanisavljević, Danijela and Ivanov, Marija and Vasiljević, Perica and Stevanović, Milena and Soković, Marina and Stojković, Dejan",
year = "2019",
abstract = "Pyrimethanil, a synthetic fungicide widely used for the treatment of pre‐ and postharvest fungal diseases on different agricultural crops, was explored for its antifungal activity on different fungal strains. The effect of pyrimethanil on fungal ergosterol was tested by using Aspergillus niger as a model organism. Furthermore, it was investigated, if pyrimethanil can effectively reduce the appearance of Aspergillus rot in wounded cherry tomato fruits. The fungicide cytotoxic effect on different human cell lines was evaluated. In addition, its influence on cell proliferation was studied. A. niger was the most resistant fungal strain (MFC 1.88 μg μL−1) to the effect of pyrimethanil. Addition of ergosterol doubled the MFC on A. niger, indicating that the compound might interfere with ergosterol, main sterol of fungal cell membrane. Disease incidence of A. niger in wounded cherry tomato fruits was not detected with pyrimethanil treatment of 0.75 mg/wound. Some cytotoxic effects of pyrimethanil on human cell lines were recorded already at 50 ng μL−1, while the expression of Ki67 marker of proliferation was decreased with 150 ng μL−1. These results altogether indicate that pyrimethanil is effective in reducing various fungal pathogens, but further use of this fungicide should be reevaluated because of its cytotoxicity.",
journal = "Annals of Applied Biology",
title = "Pyrimethanil: Between efficient fungicide against Aspergillus rot on cherry tomato and cytotoxic agent on human cell lines",
number = "2",
volume = "175",
doi = "10.1111/aab.12532",
pages = "228-235"
}
Aleksić, M., Stanisavljević, D., Ivanov, M., Vasiljević, P., Stevanović, M., Soković, M.,& Stojković, D.. (2019). Pyrimethanil: Between efficient fungicide against Aspergillus rot on cherry tomato and cytotoxic agent on human cell lines. in Annals of Applied Biology, 175(2), 228-235.
https://doi.org/10.1111/aab.12532
Aleksić M, Stanisavljević D, Ivanov M, Vasiljević P, Stevanović M, Soković M, Stojković D. Pyrimethanil: Between efficient fungicide against Aspergillus rot on cherry tomato and cytotoxic agent on human cell lines. in Annals of Applied Biology. 2019;175(2):228-235.
doi:10.1111/aab.12532 .
Aleksić, Milena, Stanisavljević, Danijela, Ivanov, Marija, Vasiljević, Perica, Stevanović, Milena, Soković, Marina, Stojković, Dejan, "Pyrimethanil: Between efficient fungicide against Aspergillus rot on cherry tomato and cytotoxic agent on human cell lines" in Annals of Applied Biology, 175, no. 2 (2019):228-235,
https://doi.org/10.1111/aab.12532 . .
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Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's Disease Are Associated with Altered Expression of SOXB Transcription Factors.

Zaletel, Ivan; Schwirtlich, Marija; Perović, Milka; Jovanović, Mirna; Stevanović, Milena; Kanazir, Selma; Puškaš, Nela

(2018)

TY  - JOUR
AU  - Zaletel, Ivan
AU  - Schwirtlich, Marija
AU  - Perović, Milka
AU  - Jovanović, Mirna
AU  - Stevanović, Milena
AU  - Kanazir, Selma
AU  - Puškaš, Nela
PY  - 2018
UR  - http://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/JAD-180277
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3149
AB  - Dysregulation of neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus has been related to cognitive deficits and memory loss in neurodegenerative diseases, such as Alzheimer's disease (AD). Members of the B group of SOX transcription factors play critical roles in regulating neurogenesis in the embryonic and adult nervous system, including maintaining the multipotency, renewal, and cell fate decision of neural stem/progenitor cells. The aim of the present study was to evaluate the expression patterns of selected SOXB proteins in the SGZ, of 8-week-old male and female 5xFAD mice, which represent a transgenic model of AD with a severe and very early development of amyloid pathology. Immunohistochemical analysis showed a significant decrease in the number of cells expressing SOX1, SOX2, and SOX21 transcription factors within the SGZ of 5xFAD mice in comparison to their non-transgenic counterparts which coincidences with reduced number of doublecortin immunoreactive immature neurons found in Tg males. Despite observed changes in expressional pattern of examined SOXB proteins, the proliferative capacity evaluated by the number of Ki-67 immunoreactive cells remained unaffected in transgenic mice of both genders. Based on our results, we suggest that SOXB proteins might be considered as new biomarkers for the detection of early impairments in adult neurogenesis in different animal models or/and new targets in human regenerative medicine.
T2  - Journal of Alzheimer's Disease : JAD
T1  - Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's Disease Are Associated with Altered Expression of SOXB Transcription Factors.
IS  - 3
VL  - 65
DO  - 10.3233/JAD-180277
SP  - 963
EP  - 976
ER  - 
@article{
author = "Zaletel, Ivan and Schwirtlich, Marija and Perović, Milka and Jovanović, Mirna and Stevanović, Milena and Kanazir, Selma and Puškaš, Nela",
year = "2018",
abstract = "Dysregulation of neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus has been related to cognitive deficits and memory loss in neurodegenerative diseases, such as Alzheimer's disease (AD). Members of the B group of SOX transcription factors play critical roles in regulating neurogenesis in the embryonic and adult nervous system, including maintaining the multipotency, renewal, and cell fate decision of neural stem/progenitor cells. The aim of the present study was to evaluate the expression patterns of selected SOXB proteins in the SGZ, of 8-week-old male and female 5xFAD mice, which represent a transgenic model of AD with a severe and very early development of amyloid pathology. Immunohistochemical analysis showed a significant decrease in the number of cells expressing SOX1, SOX2, and SOX21 transcription factors within the SGZ of 5xFAD mice in comparison to their non-transgenic counterparts which coincidences with reduced number of doublecortin immunoreactive immature neurons found in Tg males. Despite observed changes in expressional pattern of examined SOXB proteins, the proliferative capacity evaluated by the number of Ki-67 immunoreactive cells remained unaffected in transgenic mice of both genders. Based on our results, we suggest that SOXB proteins might be considered as new biomarkers for the detection of early impairments in adult neurogenesis in different animal models or/and new targets in human regenerative medicine.",
journal = "Journal of Alzheimer's Disease : JAD",
title = "Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's Disease Are Associated with Altered Expression of SOXB Transcription Factors.",
number = "3",
volume = "65",
doi = "10.3233/JAD-180277",
pages = "963-976"
}
Zaletel, I., Schwirtlich, M., Perović, M., Jovanović, M., Stevanović, M., Kanazir, S.,& Puškaš, N.. (2018). Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's Disease Are Associated with Altered Expression of SOXB Transcription Factors.. in Journal of Alzheimer's Disease : JAD, 65(3), 963-976.
https://doi.org/10.3233/JAD-180277
Zaletel I, Schwirtlich M, Perović M, Jovanović M, Stevanović M, Kanazir S, Puškaš N. Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's Disease Are Associated with Altered Expression of SOXB Transcription Factors.. in Journal of Alzheimer's Disease : JAD. 2018;65(3):963-976.
doi:10.3233/JAD-180277 .
Zaletel, Ivan, Schwirtlich, Marija, Perović, Milka, Jovanović, Mirna, Stevanović, Milena, Kanazir, Selma, Puškaš, Nela, "Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's Disease Are Associated with Altered Expression of SOXB Transcription Factors." in Journal of Alzheimer's Disease : JAD, 65, no. 3 (2018):963-976,
https://doi.org/10.3233/JAD-180277 . .
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Apigenin-7-O-glucoside versus apigenin: Insight into the modes of anticandidal and cytotoxic actions

Ivanov, Marija; Stanisavljević, Danijela; Stojković, Dejan; Petrović, Isidora; Vićentić Marjanović, Jelena; Popović, Jelena; Golić Grdadolnik, Simona; Marković, Dejan; Sanković-Babić, Snežana; Glamočlija, Jasmina; Stevanović, Milena; Soković, Marina

(2017)

TY  - JOUR
AU  - Ivanov, Marija
AU  - Stanisavljević, Danijela
AU  - Stojković, Dejan
AU  - Petrović, Isidora
AU  - Vićentić Marjanović, Jelena
AU  - Popović, Jelena
AU  - Golić Grdadolnik, Simona
AU  - Marković, Dejan
AU  - Sanković-Babić, Snežana
AU  - Glamočlija, Jasmina
AU  - Stevanović, Milena
AU  - Soković, Marina
PY  - 2017
UR  - http://www.excli.de/vol16/Sokovic_23052017_proof.pdf
UR  - http://www.excli.de/volume16.php
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2791
AB  - Bioactive potential of apigenin derivative apigenin-7-O-glucoside related to its antifungal activity on Candida spp. and cytotoxic effect on colon cancer cells was studied and compared with bioactive potential of apigenin. Antifungal activity was tested on 14 different isolates of Candida spp. using membrane permeability assay, measuring inhibition of reactive oxidative species and inhibition of CYP51 C. albicans enzyme. Cytotoxic potential of apigenin- 7-O-glucoside was tested on colon cancer HCT116 cells by measuring cell viability, apoptosis rate and apoptosis- and colon cancer-related gene expression. Obtained results indicated considerable antifungal activity of apigenin-7-O-glucoside towards all Candida isolates. Breakdown of C. albicans plasma membrane was achieved upon treatment with apigenin-7-O-glucoside for shorter period of time then with apigenin. Reduction of intra- and extracellular reactive oxidative species was achieved with minimum inhibitory concentrations of both compounds, suggesting that reactive oxidative species inhibition could be a mechanism of antifungal action. None of the compounds exhibited binding affinity to C. albicans CYP51 protein. Besides, apigenin-7-O-glucoside was more effective compared to apigenin in reduction of cell’s viability and induction of cell death of HCT116 cells. Treatment with both compounds resulted in chromatin condensation, apoptotic bodies formation and apoptotic genes expression in HCT116 cells, but the apigenin-7-O-glucoside required a lower concentration to achieve the same effect. Compounds apigenin-7-O-glucoside and apigenin displayed prominent antifungal potential and cytotoxic effect on HCT116 cells. However, our results showed that apigenin-7-O-glucoside has more potent activity compared to apigenin in all assays that we used.
T2  - EXCLI Journal
T1  - Apigenin-7-O-glucoside versus apigenin: Insight into the modes of anticandidal and cytotoxic actions
VL  - 16
DO  - 10.17179/excli2017-300
SP  - 795
EP  - 807
ER  - 
@article{
author = "Ivanov, Marija and Stanisavljević, Danijela and Stojković, Dejan and Petrović, Isidora and Vićentić Marjanović, Jelena and Popović, Jelena and Golić Grdadolnik, Simona and Marković, Dejan and Sanković-Babić, Snežana and Glamočlija, Jasmina and Stevanović, Milena and Soković, Marina",
year = "2017",
abstract = "Bioactive potential of apigenin derivative apigenin-7-O-glucoside related to its antifungal activity on Candida spp. and cytotoxic effect on colon cancer cells was studied and compared with bioactive potential of apigenin. Antifungal activity was tested on 14 different isolates of Candida spp. using membrane permeability assay, measuring inhibition of reactive oxidative species and inhibition of CYP51 C. albicans enzyme. Cytotoxic potential of apigenin- 7-O-glucoside was tested on colon cancer HCT116 cells by measuring cell viability, apoptosis rate and apoptosis- and colon cancer-related gene expression. Obtained results indicated considerable antifungal activity of apigenin-7-O-glucoside towards all Candida isolates. Breakdown of C. albicans plasma membrane was achieved upon treatment with apigenin-7-O-glucoside for shorter period of time then with apigenin. Reduction of intra- and extracellular reactive oxidative species was achieved with minimum inhibitory concentrations of both compounds, suggesting that reactive oxidative species inhibition could be a mechanism of antifungal action. None of the compounds exhibited binding affinity to C. albicans CYP51 protein. Besides, apigenin-7-O-glucoside was more effective compared to apigenin in reduction of cell’s viability and induction of cell death of HCT116 cells. Treatment with both compounds resulted in chromatin condensation, apoptotic bodies formation and apoptotic genes expression in HCT116 cells, but the apigenin-7-O-glucoside required a lower concentration to achieve the same effect. Compounds apigenin-7-O-glucoside and apigenin displayed prominent antifungal potential and cytotoxic effect on HCT116 cells. However, our results showed that apigenin-7-O-glucoside has more potent activity compared to apigenin in all assays that we used.",
journal = "EXCLI Journal",
title = "Apigenin-7-O-glucoside versus apigenin: Insight into the modes of anticandidal and cytotoxic actions",
volume = "16",
doi = "10.17179/excli2017-300",
pages = "795-807"
}
Ivanov, M., Stanisavljević, D., Stojković, D., Petrović, I., Vićentić Marjanović, J., Popović, J., Golić Grdadolnik, S., Marković, D., Sanković-Babić, S., Glamočlija, J., Stevanović, M.,& Soković, M.. (2017). Apigenin-7-O-glucoside versus apigenin: Insight into the modes of anticandidal and cytotoxic actions. in EXCLI Journal, 16, 795-807.
https://doi.org/10.17179/excli2017-300
Ivanov M, Stanisavljević D, Stojković D, Petrović I, Vićentić Marjanović J, Popović J, Golić Grdadolnik S, Marković D, Sanković-Babić S, Glamočlija J, Stevanović M, Soković M. Apigenin-7-O-glucoside versus apigenin: Insight into the modes of anticandidal and cytotoxic actions. in EXCLI Journal. 2017;16:795-807.
doi:10.17179/excli2017-300 .
Ivanov, Marija, Stanisavljević, Danijela, Stojković, Dejan, Petrović, Isidora, Vićentić Marjanović, Jelena, Popović, Jelena, Golić Grdadolnik, Simona, Marković, Dejan, Sanković-Babić, Snežana, Glamočlija, Jasmina, Stevanović, Milena, Soković, Marina, "Apigenin-7-O-glucoside versus apigenin: Insight into the modes of anticandidal and cytotoxic actions" in EXCLI Journal, 16 (2017):795-807,
https://doi.org/10.17179/excli2017-300 . .
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