o:31328 Rescuing hamster fibrosarcoma growth by stimulation of different prooncogenic signaling pathways relative to repurposed anticancer drug mechanisms en Abstract: Many drugs registered for various non-oncological indications influence tumor metabolic processes, signaling pathways, enzymes, proteins, tumor receptors and genes that regulate proliferation, neoangiogenesis, apoptosis and necroptosis, without affecting these activities in healthy cells. The aim: Detecting underlying anticancer mechanism of metformin in two-drug combinations with other repurposed drugs (2-Deoxy-D-glucose, deoxycholic acid, caffeine, itraconazole or disulfiram) by rescuing BHK-21/C13 hamster fibrosarcoma growth with glucose, vitamin C, nitroglycerin or mebendazole. Methods: The anticancer mechanisms of examined drug combinations, <50% LD50 (equivalent to usual human dose), were determined by rescuing fibrosarcoma growth with addition of aforementioned agents in treatment. Immunohistochemical markers (Ki-67, PCNA, CD34, CD31, GLUT1, iNOS, COX4, Cytochrome C) in control and experimental groups were assessed 19 days after BHK-21/C13 tumor inoculation. Tumors were excised, measured and blood collected. Biophysical, pathohistological, toxicological, hematological, biochemical and statistical analyses were performed. Results: Only addition of NF-kB stimulator mebendazole to effective two-drug combinations containing metformin rescued cancer growth, indicating that this pathway may be responsible for antitumor action. Conclusion: NF-kB signaling pathway downregulation plays an essential role among anticancer mechanisms of investigated metformin combinations in hamster fibrosarcoma treatment. Keywords : fibrosarcoma; hamster; repurposed drugs; anticancer mechanism. 1552100 978-86-7078-173-3 1552102 https://indico.bio.bg.ac.rs/event/4/attachments/6/492/Abstract%20Book-CoMBoS2-TMB.pdf 2023-10-20T13:59:30.706Z 44 no 46 Kosta J. Popović 0000-0001-7895-9009 Dušica J. Popović Državni univerzitet u Novom Pazaru person 0000-0001-7880-0874 Dejan Miljković person 0000-0002-7739-5202 Dušan Lalošević person 0000-0002-0760-9180 Ivan Čapo person 0000-0001-7531-5099 Mihalj Poša person 0000-0002-8044-2655 Zana Dolićanin Državni univerzitet u Novom Pazaru person 2237799 0000-0003-0457-3087 Jovan K. Popović person 0000-0002-6790-8668 application/pdf 397039 https://phaidrabg.bg.ac.rs/o:31328 no yes 1 70 92000004 20A01 Serbian Society for Molecular Biology, CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, 06-08 October 2023, Belgrade, Serbia. Abstract Book – Trends in Molecular Biology, Special issue 2 42 42 2023