Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model
2022
Аутори:
Krajnović, TamaraDrača, Dijana
Kaluđerović, Goran N.
Dunđerović, Duško
Mirkov, Ivana
Wessjohann, Ludger A.
Maksimović-Ivanić, Danijela
Mijatović, Sanja
Остала ауторства
Arsenijević, NebojšaТип документа:
Конференцијски прилог (Објављена верзија)
,
© 2022 by the Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
Метаподаци
Приказ свих података о документуАпстракт:
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.
Кључне речи:
melanoma; prenylflavonid; chemotherapy; adhesion; migration; invasion; chemosensitization; differentiationФинансирање / пројекти:
- Ministry of Education, Science and Technological Development of the Republic of Serbia
- Leibniz Institute of Plant Biochemistry, Halle, from the German Academic Exchange Service (DAAD)
- Hopsteiner (Simon H. Steiner Hopfen GmbH)
У:
- Arsenijević N, editor. Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine; 2022. p. 152-3.