Digitalni repozitorijum
Univerziteta u Beogradu
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ROS and NF-kB role in repurposed drugs treatment of hamster fibrosarcoma
Lalošević, Dušan
Čapo, Ivan
Popović, Jovan K.
Popović, Kosta J.
Dolićanin, Zana
Popović, Dušica J.
Poša, Mihalj
Abstract: The NF-kB activity in cancer cells promotes tumor growth by stimulation of cell proliferation, neoangiogenesis and by inhibition of apoptosis and ROS activity. Anticancer combinations of two repurposed drugs: metformin with 2-Deoxy-D-glucose, deoxycholic acid, caffeine, itraconazole or disulfiram (<50% LD50, equivalent to usual human dose) mechanism of action was investigated by rescuing treated BHK-21/C13 fibrosarcoma growth in hamsters with ROS inhibitor nitroglycerin and NF-kB stimulator mebendazole. 19 days after inoculation, anticancer effects were assessed by biophysical measurements of fibrosarcoma growth and immunohistochemical markers of tumor proliferation (Ki-67, PCNA), neoangiogenesis (CD34, CD31), glucose metabolism (GLUT1), NO metabolism (iNOS) and apoptosis (COX4, Cytochrome C). The combinations have shown significant antitumor effects (P<0.05) which were inhibited partly by addition of ROS inhibitor nitroglycerin and completely by NF-kB stimulator mebendazole. Results indicate NF-kB key role in anticancer action of investigated drug combinations of non-oncological drugs and their potential to be used in oncology.
engleski
2023
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