Stimulation and inhibition of NF-B by repurposed drugs – effects on hamster fibrosarcoma
Popović J., Kosta
Lalošević, Dušan
Popović K., Jovan
Popović J., Dušica
Miljković, Dejan
Dolićanin, Zana
Čapo, Ivan
Abstract: Background. NF-B transcription factors are key regulators of apoptosis, autophagy, necroptosis and turns up everywhere in cancer life and death. This study investigated how the regulation of NF-B by repurposed drugs in oncology affect experimental fibrosarcoma development and progression in hamsters. Material and Methods. Anticancer efficacy of certain drugs was tested on fibrosarcoma experimentally induced by BHK21/C13 cells in Syrian golden hamsters. Used repurposed drugs with in vitro verified NF-B inhibitory effect were: metformin, caffeine, itraconazole, nitroglycerin. Used drug with known NF-B stimulatory effect was mebendazole. Tumor biophysical characteristics, histology and immunohistochemistry were assessed. Blood samples were collected for hematological and biochemical analyses and the main organs were toxicologically analyzed. Results. Our study showed that combinations of NF-B inhibitors: metformin with caffeine, metformin with itraconazole and metformin with nitroglycerin, in human equivalent doses could be efficaceous (P < 0.05) against fibrosarcoma growth, which can rescued by mebendazole, without toxicity and influence on biochemical and hematological tests. Conclusion. Combinations of repurposed drugs with NF-B inhibitory effect: metformin with caffeine, metformin with itraconazole and metformin with nitroglycerin could be an important therapeutic option in oncology.
engleski
2023
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Keywords : BHK-21/C13 cell culture, drug effects, fibrosarcoma, hamsters, NF-kB