TY  - JOUR
AU  - Mihajlović, Ekatarina
AU  - Biancalana, Lorenzo
AU  - Jelača, Sanja
AU  - Chiaverini, Lorenzo
AU  - Dojčinović, Biljana
AU  - Dunđerović, Duško
AU  - Zacchini, Stefano
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Marchetti, Fabio
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6701
AB  - FETPY, an organo-diiron(I) complex, showed strong cytotoxicity across a panel of human and mouse cancer cell lines, combined with an outstanding selectivity compared to nonmalignant cells. Enhanced iron uptake in aggressive, low-differentiated cell lines, caused membrane lipid peroxidation, which resulted in ferroptosis in human ovarian cancer cells. FETPY induced significant morphological changes in murine B16–F1 and B16–F10 melanoma cells, leading to senescence and/or trans-differentiation into Schwann-like cells, thus significantly reducing their tumorigenic potential. Additionally, FETPY substantially suppressed tumor growth in low- and high-grade syngeneic melanoma models when administered in a therapeutic regimen. FETPY is featured by satisfactory water solubility (millimolar range), an amphiphilic character (Log Pow = −0.17), and excellent stability in a biological medium (DMEM). These important requisites for drug development are rarely met in iron complexes investigated so far as possible anticancer agents. Overall, FETPY holds promise as a safe and potent targeted antitumor agent.
PB  - American Chemical Society
T2  - Journal of Medicinal Chemistry
T1  - FETPY: a Diiron(I) Thio–Carbyne Complex with Prominent Anticancer Activity In Vitro and In Vivo
IS  - 9
VL  - 67
DO  - 10.1021/acs.jmedchem.4c00377
SP  - 7553
EP  - 7568
ER  - 

@article{
author = "Mihajlović, Ekatarina and Biancalana, Lorenzo and Jelača, Sanja and Chiaverini, Lorenzo and Dojčinović, Biljana and Dunđerović, Duško and Zacchini, Stefano and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Marchetti, Fabio",
year = "2024",
abstract = "FETPY, an organo-diiron(I) complex, showed strong cytotoxicity across a panel of human and mouse cancer cell lines, combined with an outstanding selectivity compared to nonmalignant cells. Enhanced iron uptake in aggressive, low-differentiated cell lines, caused membrane lipid peroxidation, which resulted in ferroptosis in human ovarian cancer cells. FETPY induced significant morphological changes in murine B16–F1 and B16–F10 melanoma cells, leading to senescence and/or trans-differentiation into Schwann-like cells, thus significantly reducing their tumorigenic potential. Additionally, FETPY substantially suppressed tumor growth in low- and high-grade syngeneic melanoma models when administered in a therapeutic regimen. FETPY is featured by satisfactory water solubility (millimolar range), an amphiphilic character (Log Pow = −0.17), and excellent stability in a biological medium (DMEM). These important requisites for drug development are rarely met in iron complexes investigated so far as possible anticancer agents. Overall, FETPY holds promise as a safe and potent targeted antitumor agent.",
publisher = "American Chemical Society",
journal = "Journal of Medicinal Chemistry",
title = "FETPY: a Diiron(I) Thio–Carbyne Complex with Prominent Anticancer Activity In Vitro and In Vivo",
number = "9",
volume = "67",
doi = "10.1021/acs.jmedchem.4c00377",
pages = "7553-7568"
}

Mihajlović, E., Biancalana, L., Jelača, S., Chiaverini, L., Dojčinović, B., Dunđerović, D., Zacchini, S., Mijatović, S., Maksimović-Ivanić, D.,& Marchetti, F.. (2024). FETPY: a Diiron(I) Thio–Carbyne Complex with Prominent Anticancer Activity In Vitro and In Vivo. in Journal of Medicinal Chemistry
American Chemical Society., 67(9), 7553-7568.
https://doi.org/10.1021/acs.jmedchem.4c00377

Mihajlović E, Biancalana L, Jelača S, Chiaverini L, Dojčinović B, Dunđerović D, Zacchini S, Mijatović S, Maksimović-Ivanić D, Marchetti F. FETPY: a Diiron(I) Thio–Carbyne Complex with Prominent Anticancer Activity In Vitro and In Vivo. in Journal of Medicinal Chemistry. 2024;67(9):7553-7568.
doi:10.1021/acs.jmedchem.4c00377 .

Mihajlović, Ekatarina, Biancalana, Lorenzo, Jelača, Sanja, Chiaverini, Lorenzo, Dojčinović, Biljana, Dunđerović, Duško, Zacchini, Stefano, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Marchetti, Fabio, "FETPY: a Diiron(I) Thio–Carbyne Complex with Prominent Anticancer Activity In Vitro and In Vivo" in Journal of Medicinal Chemistry, 67, no. 9 (2024):7553-7568,
https://doi.org/10.1021/acs.jmedchem.4c00377 . .

TY  - JOUR
AU  - Jelača, Sanja
AU  - Jovanović, Ivan
AU  - Bovan, Dijana
AU  - Jovanović, Marina Z.
AU  - Jurišević, Milena M.
AU  - Dunđerović, Duško
AU  - Dajić-Stevanović, Zora
AU  - Arsenijević, Nebojša
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6575
AB  - Ethnomedicinal records have long mentioned the historical usage of Alchemilla vulgaris L. in folk medicine, particularly for the treatment of gynecological issues. Building on this ethnomedicinal knowledge regarding female illnesses, the aim of this research was to evaluate the impact of ethanolic extract of A. vulgaris on mouse breast cancer cells (4T1) in vitro and in vivo, in addition to its effect on the immune compartment in the tumor microenvironment. Behind viability decrease of 4T1 cells induced by treatment with A. vulgaris extract was strong inhibition of cell proliferation accompanied by caspase-dependent apoptosis and autophagic cell death. Observed changes in 4T1 cell culture after treatment were well orchestrated and led to a reduction in metastatic potential through weakened adhesion, invasion, migration, and colony-forming abilities in vitro. Enhanced intracellular production of reactive oxygen and nitrogen species promoted by the treatment might interfere with all the observed effects. Apart from the direct effect on tumor cells, the A. vulgaris extract significantly reduced tumor growth in the solid orthotropic mammary carcinoma model through restitution of efficient local and systemic immune response reflected in enhanced antigen-presenting potential of dendritic cells (DCs) as well as the extent and activity of effector T cells.
PB  - Basel: MDPI
T2  - Pharmaceuticals
T1  - Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response
IS  - 3
VL  - 17
DO  - 10.3390/ph17030286
SP  - 286
ER  - 

@article{
author = "Jelača, Sanja and Jovanović, Ivan and Bovan, Dijana and Jovanović, Marina Z. and Jurišević, Milena M. and Dunđerović, Duško and Dajić-Stevanović, Zora and Arsenijević, Nebojša and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2024",
abstract = "Ethnomedicinal records have long mentioned the historical usage of Alchemilla vulgaris L. in folk medicine, particularly for the treatment of gynecological issues. Building on this ethnomedicinal knowledge regarding female illnesses, the aim of this research was to evaluate the impact of ethanolic extract of A. vulgaris on mouse breast cancer cells (4T1) in vitro and in vivo, in addition to its effect on the immune compartment in the tumor microenvironment. Behind viability decrease of 4T1 cells induced by treatment with A. vulgaris extract was strong inhibition of cell proliferation accompanied by caspase-dependent apoptosis and autophagic cell death. Observed changes in 4T1 cell culture after treatment were well orchestrated and led to a reduction in metastatic potential through weakened adhesion, invasion, migration, and colony-forming abilities in vitro. Enhanced intracellular production of reactive oxygen and nitrogen species promoted by the treatment might interfere with all the observed effects. Apart from the direct effect on tumor cells, the A. vulgaris extract significantly reduced tumor growth in the solid orthotropic mammary carcinoma model through restitution of efficient local and systemic immune response reflected in enhanced antigen-presenting potential of dendritic cells (DCs) as well as the extent and activity of effector T cells.",
publisher = "Basel: MDPI",
journal = "Pharmaceuticals",
title = "Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response",
number = "3",
volume = "17",
doi = "10.3390/ph17030286",
pages = "286"
}

Jelača, S., Jovanović, I., Bovan, D., Jovanović, M. Z., Jurišević, M. M., Dunđerović, D., Dajić-Stevanović, Z., Arsenijević, N., Mijatović, S.,& Maksimović-Ivanić, D.. (2024). Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response. in Pharmaceuticals
Basel: MDPI., 17(3), 286.
https://doi.org/10.3390/ph17030286

Jelača S, Jovanović I, Bovan D, Jovanović MZ, Jurišević MM, Dunđerović D, Dajić-Stevanović Z, Arsenijević N, Mijatović S, Maksimović-Ivanić D. Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response. in Pharmaceuticals. 2024;17(3):286.
doi:10.3390/ph17030286 .

Jelača, Sanja, Jovanović, Ivan, Bovan, Dijana, Jovanović, Marina Z., Jurišević, Milena M., Dunđerović, Duško, Dajić-Stevanović, Zora, Arsenijević, Nebojša, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response" in Pharmaceuticals, 17, no. 3 (2024):286,
https://doi.org/10.3390/ph17030286 . .

TY  - CONF
AU  - Krajnović, Tamara
AU  - Drača, Dijana
AU  - Kaluđerović, Goran N.
AU  - Dunđerović, Duško
AU  - Mirkov, Ivana
AU  - Wessjohann, Ludger A.
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5291
AB  - A prenylflavonoid from hops, isoxanthohumol (IXN) is gaining a lot of attention
nowadays due to its broad spectrum of biological activities. This study aimed to investigate
its potential antimetastatic properties in vitro against the highly invasive melanoma
cell line B16-F10 and in a murine metastatic model in vivo, in the context of
independent action and interaction with chemotherapy. The treatment with IXN diminished
cell viability in a dose-dependent manner, which is a consequence of induced
combined cell death by autophagy and caspase-dependent apoptosis. Additionally, the
dividing potential of highly proliferative melanoma cells was dramatically affected by
IXN, and is in line with an abrogated clonogenic potential in the population of survived
cells, indicating changes in their metastatic features. Concordantly, IXN strongly diminished
cell metastatic features down-regulating adhesion, migration, and invasion
through disrupted integrin signaling. Separate application of IXN inhibited the development
of lung metastatic foci in tumor-challenged animals. Although IXN potentiated
the action of chemotherapeutic drug paclitaxel (PCT) in vitro, the concomitant
treatment of these two agents did not exert statistically significant suppression of lung
metastases formation. Nonetheless, the change in the regime of drugs’ application to
7-day treatment with IXN prior to PCT made the subtherapeutic dose of PCT effective,
indicating IXNs’ capacity to trigger the differentiation of B16-F10 cells toward a less
invasive phenotype, thus sensitizing them to chemotherapy. Along with histopathological
confirmation of changes in cell phenotype in metastases, this data underlines the
important impact of the differentiation process on chemotherapy efficacy. This study
represents the first proof of IXNs’ antimetastatic activity in vivo and significantly contributes
to the development of the differentiation therapy concept as a support in the
treatment of metastatic malignancies.
AB  - Пренилфлавоноид из хмеља, изоксантохумол (IXN) данас привлачи велику
пажњу због свог широког спектра биолошких активности. Ова студија је имала
за циљ да истражи његова потенцијална антиметастатска својства на високо ин-
вазивној ћелијској линији меланома B16-F10 in vitro и in vivo, у контексту њего-
вог самосталног деловања или у комбинацији са хемотерапијом. Третман IXN је
смањио вијабилитет ћелија меланома на дозно зависан начин, што је последица
индуковане комбиноване ћелијске смрти аутофагијом и апоптозом зависном од
каспаза. Поред тога, овај изофлаванон је снажно инхибирао деобу високо про-
лиферативних ћелија меланома као и клоногени потенцијал преживелих ћели-
ја, указујући на промене у њиховим метастатским карактеристикама. Сагласно
томе, IXN је супримирао процесе који дефинишу метастазирање као што су
ћелијска адхезија, миграција и инвазија, ометајући интегрински сигнални пут.
Примена IXN је инхибирала развој метастатских жаришта у плућима експери-
менталних животиња. Иако је IXN појачао дејство хемотерапеутика паклитаксе-
ла (PCT) in vitro, истовремени третман ова два агенса није довео до статистички
значајне супресије у формирању плућних метастаза. Са друге стране, промена
динамике давања агенаса у виду 7-дневног третмана животиња IXN пре апли-
кације PCT учинила је ефикасном субтерапеутску дозу PCT, што се може при-
писати његовом капацитету да диферентује B16-F10 ћелије ка мање инвазивном
фенотипу и тиме их сензитизује на хемотерапију. Уз хистопатолошку потврду
промене фенотипа ћелија у метастазама, овај податак указује на значајан до-
принос процеса диференцијације успешности исхода хемотерапије. Ова студија
представља први доказ антиметастатске активности IXN in vivo и значајно до-
приноси успостављању концепта диференцијационе терапије у подршци лечењу
метастатских малигнитета.
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  - Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model
SP  - 152
EP  - 153
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5291
ER  - 

@conference{
author = "Krajnović, Tamara and Drača, Dijana and Kaluđerović, Goran N. and Dunđerović, Duško and Mirkov, Ivana and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela and Mijatović, Sanja",
year = "2022",
abstract = "A prenylflavonoid from hops, isoxanthohumol (IXN) is gaining a lot of attention
nowadays due to its broad spectrum of biological activities. This study aimed to investigate
its potential antimetastatic properties in vitro against the highly invasive melanoma
cell line B16-F10 and in a murine metastatic model in vivo, in the context of
independent action and interaction with chemotherapy. The treatment with IXN diminished
cell viability in a dose-dependent manner, which is a consequence of induced
combined cell death by autophagy and caspase-dependent apoptosis. Additionally, the
dividing potential of highly proliferative melanoma cells was dramatically affected by
IXN, and is in line with an abrogated clonogenic potential in the population of survived
cells, indicating changes in their metastatic features. Concordantly, IXN strongly diminished
cell metastatic features down-regulating adhesion, migration, and invasion
through disrupted integrin signaling. Separate application of IXN inhibited the development
of lung metastatic foci in tumor-challenged animals. Although IXN potentiated
the action of chemotherapeutic drug paclitaxel (PCT) in vitro, the concomitant
treatment of these two agents did not exert statistically significant suppression of lung
metastases formation. Nonetheless, the change in the regime of drugs’ application to
7-day treatment with IXN prior to PCT made the subtherapeutic dose of PCT effective,
indicating IXNs’ capacity to trigger the differentiation of B16-F10 cells toward a less
invasive phenotype, thus sensitizing them to chemotherapy. Along with histopathological
confirmation of changes in cell phenotype in metastases, this data underlines the
important impact of the differentiation process on chemotherapy efficacy. This study
represents the first proof of IXNs’ antimetastatic activity in vivo and significantly contributes
to the development of the differentiation therapy concept as a support in the
treatment of metastatic malignancies., Пренилфлавоноид из хмеља, изоксантохумол (IXN) данас привлачи велику
пажњу због свог широког спектра биолошких активности. Ова студија је имала
за циљ да истражи његова потенцијална антиметастатска својства на високо ин-
вазивној ћелијској линији меланома B16-F10 in vitro и in vivo, у контексту њего-
вог самосталног деловања или у комбинацији са хемотерапијом. Третман IXN је
смањио вијабилитет ћелија меланома на дозно зависан начин, што је последица
индуковане комбиноване ћелијске смрти аутофагијом и апоптозом зависном од
каспаза. Поред тога, овај изофлаванон је снажно инхибирао деобу високо про-
лиферативних ћелија меланома као и клоногени потенцијал преживелих ћели-
ја, указујући на промене у њиховим метастатским карактеристикама. Сагласно
томе, IXN је супримирао процесе који дефинишу метастазирање као што су
ћелијска адхезија, миграција и инвазија, ометајући интегрински сигнални пут.
Примена IXN је инхибирала развој метастатских жаришта у плућима експери-
менталних животиња. Иако је IXN појачао дејство хемотерапеутика паклитаксе-
ла (PCT) in vitro, истовремени третман ова два агенса није довео до статистички
значајне супресије у формирању плућних метастаза. Са друге стране, промена
динамике давања агенаса у виду 7-дневног третмана животиња IXN пре апли-
кације PCT учинила је ефикасном субтерапеутску дозу PCT, што се може при-
писати његовом капацитету да диферентује B16-F10 ћелије ка мање инвазивном
фенотипу и тиме их сензитизује на хемотерапију. Уз хистопатолошку потврду
промене фенотипа ћелија у метастазама, овај податак указује на значајан до-
принос процеса диференцијације успешности исхода хемотерапије. Ова студија
представља први доказ антиметастатске активности IXN in vivo и значајно до-
приноси успостављању концепта диференцијационе терапије у подршци лечењу
метастатских малигнитета.",
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 = "Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model",
pages = "152-153",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5291"
}

Krajnović, T., Drača, D., Kaluđerović, G. N., Dunđerović, D., Mirkov, I., Wessjohann, L. A., Maksimović-Ivanić, D.,& Mijatović, S.. (2022). Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 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., 152-153.
https://hdl.handle.net/21.15107/rcub_ibiss_5291

Krajnović T, Drača D, Kaluđerović GN, Dunđerović D, Mirkov I, Wessjohann LA, Maksimović-Ivanić D, Mijatović S. Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:152-153.
https://hdl.handle.net/21.15107/rcub_ibiss_5291 .

Krajnović, Tamara, Drača, Dijana, Kaluđerović, Goran N., Dunđerović, Duško, Mirkov, Ivana, Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, Mijatović, Sanja, "Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model" in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):152-153,
https://hdl.handle.net/21.15107/rcub_ibiss_5291 .