Hopsteiner (Simon H. Steiner Hopfen GmbH)

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Hopsteiner (Simon H. Steiner Hopfen GmbH)

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Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model

Krajnović, Tamara; Drača, Dijana; Kaluđerović, Goran N.; Dunđerović, Duško; Mirkov, Ivana; Wessjohann, Ludger A.; Maksimović-Ivanić, Danijela; Mijatović, Sanja

(Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine, 2022)

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 .

The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model.

Krajnović, Tamara; Drača, Dijana; Kaluđerović, Goran; Dunđerović, Duško; Mirkov, Ivana; Wessjohann, Ludger A.; Maksimović-Ivanić, Danijela; Mijatović, Sanja

(2019)

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 . .
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