TY  - CONF
AU  - Drača, Dijana
AU  - Mijatović, Sanja
AU  - Krajnović, Tamara
AU  - Bogdanović Pristov, Jelena
AU  - Đukić, Tatjana
AU  - Kaluđerović, Goran N.
AU  - Wessjohann, Ludger A.
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5292
AB  - Tubulisins are natural peptide compounds isolated from mycobacterial genera.
They belong to the group of antimitotic agents, since they achieve their antitumor
effect disrupting the function of mitotic spindle. The object of this study was to investigate
anticancer potential of synthetic analogue of tubulysins, tubugi 1, on mouse
melanoma model, in vitro and in vivo. Tubugi 1 decreased dose-dependently viability
of B16 cells. The experimental compound induced atypical apoptosis without the externalization
of phosphatidylserines (PS). Although apoptosis was accompanied with
strong intracellular production of reactive oxygen and nitrogen species, decrease in
malonyldyaldehyde content showed that membrane lipids were not subjected to oxidation,
what is a prerequisite for the externalization of PS. Although PS plays a key
role in the removal of apoptotic cells, this did not affect the phagocytic activity of
macrophages in vitro, implying PS-independent apoptotic cells removal. The effect of
the experimental agent was confirmed in vivo. Мacrophages isolated from peritoneal
exudate of treated animals showed cytotoxic activity, what was in line with demonstrated
expression of M1 phenotype markers, as well as production of nitric oxide.
Additonally, the phagocytic activity of these cells was preserved. Having in mind lack
of data in the literature concerning the effects of this group of agents on components
of the innate immune system, tubugi 1 remains worthy of further research in the field
of experimental oncology.
AB  - Тубулизини су природна једињења изолована из родова миксобактерија.
Спадају у групу антимитотских агенаса будући да свој антитуморски ефекат
остварују на нивоу деобног вретена. У овој студији испитиван је антитумор-
ски потенцијал синтетског аналога тубулизина, тубуги 1, in vitro и in vivo на
моделу мишјег меланома. Тубуги 1 је на дозно-зависан начин смањио вијаби-
литет B16 ћелија. Експериментално једињење је у овим ћелијама индуковало
атипичну форму апоптотске ћелијске смрти без екстернализације фосфати-
дилсерина (ПС). Иако је апоптоза била праћена снажном продукцијом ре-
активних врста кисеоника и азота, смањење садржаја малонилдиалдехида је
показало да мембрански липиди нису подлегли оксидацији, што је предуслов
за екстернализацију ПС. Иако ПС има кључну улогу у уклањању апоптотских
ћелија, ово се није одразило на фагоцитну активност макрофага in vitro, ука-
зујући на фагоцитозу независну од ПС. Учинак експерименталног агенса је
потврђен in vivo. Макрофаги изоловани из перитонеалног ексудата третира-
них животиња показали су цитотоксичну активност, што је у сагласности са
показаном експресијом маркера М1 фенотипа и продукцијом азот моноксида.
Додатно, фагоцитна способност ових ћелија је била очувана. С обзиром на
недостатак података у литератури о деловању овакве групе агенаса на компо-
ненте урођеног имунског система, тубуги 1 остаје вредан даљих испитивања
на пољу експерименталне онкологије.
PB  - Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
T1  - New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model
SP  - 41
SP  - 42
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5292
ER  - 

@conference{
author = "Drača, Dijana and Mijatović, Sanja and Krajnović, Tamara and Bogdanović Pristov, Jelena and Đukić, Tatjana and Kaluđerović, Goran N. and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Tubulisins are natural peptide compounds isolated from mycobacterial genera.
They belong to the group of antimitotic agents, since they achieve their antitumor
effect disrupting the function of mitotic spindle. The object of this study was to investigate
anticancer potential of synthetic analogue of tubulysins, tubugi 1, on mouse
melanoma model, in vitro and in vivo. Tubugi 1 decreased dose-dependently viability
of B16 cells. The experimental compound induced atypical apoptosis without the externalization
of phosphatidylserines (PS). Although apoptosis was accompanied with
strong intracellular production of reactive oxygen and nitrogen species, decrease in
malonyldyaldehyde content showed that membrane lipids were not subjected to oxidation,
what is a prerequisite for the externalization of PS. Although PS plays a key
role in the removal of apoptotic cells, this did not affect the phagocytic activity of
macrophages in vitro, implying PS-independent apoptotic cells removal. The effect of
the experimental agent was confirmed in vivo. Мacrophages isolated from peritoneal
exudate of treated animals showed cytotoxic activity, what was in line with demonstrated
expression of M1 phenotype markers, as well as production of nitric oxide.
Additonally, the phagocytic activity of these cells was preserved. Having in mind lack
of data in the literature concerning the effects of this group of agents on components
of the innate immune system, tubugi 1 remains worthy of further research in the field
of experimental oncology., Тубулизини су природна једињења изолована из родова миксобактерија.
Спадају у групу антимитотских агенаса будући да свој антитуморски ефекат
остварују на нивоу деобног вретена. У овој студији испитиван је антитумор-
ски потенцијал синтетског аналога тубулизина, тубуги 1, in vitro и in vivo на
моделу мишјег меланома. Тубуги 1 је на дозно-зависан начин смањио вијаби-
литет B16 ћелија. Експериментално једињење је у овим ћелијама индуковало
атипичну форму апоптотске ћелијске смрти без екстернализације фосфати-
дилсерина (ПС). Иако је апоптоза била праћена снажном продукцијом ре-
активних врста кисеоника и азота, смањење садржаја малонилдиалдехида је
показало да мембрански липиди нису подлегли оксидацији, што је предуслов
за екстернализацију ПС. Иако ПС има кључну улогу у уклањању апоптотских
ћелија, ово се није одразило на фагоцитну активност макрофага in vitro, ука-
зујући на фагоцитозу независну од ПС. Учинак експерименталног агенса је
потврђен in vivo. Макрофаги изоловани из перитонеалног ексудата третира-
них животиња показали су цитотоксичну активност, што је у сагласности са
показаном експресијом маркера М1 фенотипа и продукцијом азот моноксида.
Додатно, фагоцитна способност ових ћелија је била очувана. С обзиром на
недостатак података у литератури о деловању овакве групе агенаса на компо-
ненте урођеног имунског система, тубуги 1 остаје вредан даљих испитивања
на пољу експерименталне онкологије.",
publisher = "Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina",
title = "New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model",
pages = "41-42",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5292"
}

Drača, D., Mijatović, S., Krajnović, T., Bogdanović Pristov, J., Đukić, T., Kaluđerović, G. N., Wessjohann, L. A.,& Maksimović-Ivanić, D.. (2022). New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 41.
https://hdl.handle.net/21.15107/rcub_ibiss_5292

Drača D, Mijatović S, Krajnović T, Bogdanović Pristov J, Đukić T, Kaluđerović GN, Wessjohann LA, Maksimović-Ivanić D. New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:41.
https://hdl.handle.net/21.15107/rcub_ibiss_5292 .

Drača, Dijana, Mijatović, Sanja, Krajnović, Tamara, Bogdanović Pristov, Jelena, Đukić, Tatjana, Kaluđerović, Goran N., Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, "New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model" in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):41,
https://hdl.handle.net/21.15107/rcub_ibiss_5292 .

TY  - JOUR
AU  - Drača, Dijana
AU  - Mijatović, Sanja
AU  - Krajnović, Tamara
AU  - Bogdanović Pristov, Jelena
AU  - Đukić, Tatjana
AU  - Kaluđerović, Goran N.
AU  - Wessjohann, Ludger A.
AU  - Maksimović-Ivanić, Danijela
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0014482719302125?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3345
AB  - Synthetic tubugis are equally potent but more stable than their natural forms. Their anticancer potential was estimated on a solid melanoma in vitro and in vivo. Tubugi-1 induced the apoptosis in B16 cells accompanied with strong intracellular production of reactive species, subsequently imposing glutathione and thiol group depletion. Paradoxically, membrane lipids were excluded from the cascade of intracellular oxidation, according to malondialdehyde decrease. Although morphologically apoptosis was typical, externalization of phosphatidylserine (PS) as an early apoptotic event was not detected. Even their exposition is pivotal for apoptotic cell eradication, primary macrophages successfully eliminated PS-deficient tubugi-1 induced apoptotic cells. The tumor volume in animals exposed to the drug in therapeutic mode was reduced in comparison to control as well as to paclitaxel-treated animals. Importantly, macrophages isolated from tubugi-1 treated animals possessed conserved phagocytic activity and were functionally and phenotypically recognized as M1. The cytotoxic effect of tubugi-1 is accomplished through its ability to polarize the macrophages toward M1, probably by PS independent apoptotic cell engulfment. The unique potential of tubugi-1 to prime the innate immune response through the induction of a specific pattern of tumor cell apoptosis can be of extraordinary importance from fundamental and applicable aspects.
T2  - Experimental Cell Research
T1  - The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model
IS  - 2
VL  - 380
DO  - 10.1016/J.YEXCR.2019.04.028
SP  - 159
EP  - 170
ER  - 

@article{
author = "Drača, Dijana and Mijatović, Sanja and Krajnović, Tamara and Bogdanović Pristov, Jelena and Đukić, Tatjana and Kaluđerović, Goran N. and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela",
year = "2019",
abstract = "Synthetic tubugis are equally potent but more stable than their natural forms. Their anticancer potential was estimated on a solid melanoma in vitro and in vivo. Tubugi-1 induced the apoptosis in B16 cells accompanied with strong intracellular production of reactive species, subsequently imposing glutathione and thiol group depletion. Paradoxically, membrane lipids were excluded from the cascade of intracellular oxidation, according to malondialdehyde decrease. Although morphologically apoptosis was typical, externalization of phosphatidylserine (PS) as an early apoptotic event was not detected. Even their exposition is pivotal for apoptotic cell eradication, primary macrophages successfully eliminated PS-deficient tubugi-1 induced apoptotic cells. The tumor volume in animals exposed to the drug in therapeutic mode was reduced in comparison to control as well as to paclitaxel-treated animals. Importantly, macrophages isolated from tubugi-1 treated animals possessed conserved phagocytic activity and were functionally and phenotypically recognized as M1. The cytotoxic effect of tubugi-1 is accomplished through its ability to polarize the macrophages toward M1, probably by PS independent apoptotic cell engulfment. The unique potential of tubugi-1 to prime the innate immune response through the induction of a specific pattern of tumor cell apoptosis can be of extraordinary importance from fundamental and applicable aspects.",
journal = "Experimental Cell Research",
title = "The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model",
number = "2",
volume = "380",
doi = "10.1016/J.YEXCR.2019.04.028",
pages = "159-170"
}

Drača, D., Mijatović, S., Krajnović, T., Bogdanović Pristov, J., Đukić, T., Kaluđerović, G. N., Wessjohann, L. A.,& Maksimović-Ivanić, D.. (2019). The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model. in Experimental Cell Research, 380(2), 159-170.
https://doi.org/10.1016/J.YEXCR.2019.04.028

Drača D, Mijatović S, Krajnović T, Bogdanović Pristov J, Đukić T, Kaluđerović GN, Wessjohann LA, Maksimović-Ivanić D. The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model. in Experimental Cell Research. 2019;380(2):159-170.
doi:10.1016/J.YEXCR.2019.04.028 .

Drača, Dijana, Mijatović, Sanja, Krajnović, Tamara, Bogdanović Pristov, Jelena, Đukić, Tatjana, Kaluđerović, Goran N., Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, "The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model" in Experimental Cell Research, 380, no. 2 (2019):159-170,
https://doi.org/10.1016/J.YEXCR.2019.04.028 . .

TY  - JOUR
AU  - Krajnović, Tamara
AU  - Drača, Dijana
AU  - Kaluđerović, Goran
AU  - Dunđerović, Duško
AU  - Mirkov, Ivana
AU  - Wessjohann, Ludger A.
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0278691519302455?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3350
AB  - Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, gained increasing attention as a potential chemopreventive agent. In the present study, IXN antimetastatic potential in vitro against the highly invasive melanoma cell line B16-F10 and in vivo in a murine metastatic model was investigated. Melanoma cell viability was diminished in a dose-dependent manner following the treatment with IXN. This decrease was a consequence of autophagy and caspase-dependent apoptosis. Additionally, the dividing potential of highly proliferative melanoma cells was dramatically affected by this isoflavanone, which was in correlation with an abrogated cell colony forming potential, indicating changes in their metastatic features. Concordantly, IXN promoted strong suppression of the processes that define metastasis- cell adhesion, invasion, and migration. Further investigation at the molecular level revealed that the abolished metastatic potential of a melanoma subclone was due to disrupted integrin signaling. Importantly, these results were reaffirmed in vivo where IXN inhibited the development of lung metastatic foci in tumor-challenged animals. The results of the present study may highlight the beneficial effects of IXN on melanoma as the most aggressive type of skin cancer and will hopefully shed a light on the possible use of this prenylflavonoid in the treatment of metastatic malignancies.
T2  - Food and Chemical Toxicology
T1  - The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model.
VL  - 129
DO  - 10.1016/j.fct.2019.04.046
SP  - 257
EP  - 268
ER  - 

@article{
author = "Krajnović, Tamara and Drača, Dijana and Kaluđerović, Goran and Dunđerović, Duško and Mirkov, Ivana and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela and Mijatović, Sanja",
year = "2019",
abstract = "Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, gained increasing attention as a potential chemopreventive agent. In the present study, IXN antimetastatic potential in vitro against the highly invasive melanoma cell line B16-F10 and in vivo in a murine metastatic model was investigated. Melanoma cell viability was diminished in a dose-dependent manner following the treatment with IXN. This decrease was a consequence of autophagy and caspase-dependent apoptosis. Additionally, the dividing potential of highly proliferative melanoma cells was dramatically affected by this isoflavanone, which was in correlation with an abrogated cell colony forming potential, indicating changes in their metastatic features. Concordantly, IXN promoted strong suppression of the processes that define metastasis- cell adhesion, invasion, and migration. Further investigation at the molecular level revealed that the abolished metastatic potential of a melanoma subclone was due to disrupted integrin signaling. Importantly, these results were reaffirmed in vivo where IXN inhibited the development of lung metastatic foci in tumor-challenged animals. The results of the present study may highlight the beneficial effects of IXN on melanoma as the most aggressive type of skin cancer and will hopefully shed a light on the possible use of this prenylflavonoid in the treatment of metastatic malignancies.",
journal = "Food and Chemical Toxicology",
title = "The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model.",
volume = "129",
doi = "10.1016/j.fct.2019.04.046",
pages = "257-268"
}

Krajnović, T., Drača, D., Kaluđerović, G., Dunđerović, D., Mirkov, I., Wessjohann, L. A., Maksimović-Ivanić, D.,& Mijatović, S.. (2019). The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model.. in Food and Chemical Toxicology, 129, 257-268.
https://doi.org/10.1016/j.fct.2019.04.046

Krajnović T, Drača D, Kaluđerović G, Dunđerović D, Mirkov I, Wessjohann LA, Maksimović-Ivanić D, Mijatović S. The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model.. in Food and Chemical Toxicology. 2019;129:257-268.
doi:10.1016/j.fct.2019.04.046 .

Krajnović, Tamara, Drača, Dijana, Kaluđerović, Goran, Dunđerović, Duško, Mirkov, Ivana, Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, Mijatović, Sanja, "The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model." in Food and Chemical Toxicology, 129 (2019):257-268,
https://doi.org/10.1016/j.fct.2019.04.046 . .