Naslov (eng)

Experimental evaluation of the effects of anticancer modulation therapy on MAPK/PI3K/AKT/mTOR/NF-B signaling with non-toxic drugs

Autor

Popović, Jovan
Popović, Dušica
Lalošević, Dušan
Popović, Kosta

Opis (eng)

Abstract: Introduction/Objective Large diversity in molecular mechanisms of cancer regulation allows some marketed pleiotropic non-oncological non-toxic pharmaceuticals to be used in oncology, which reduces duration and cost of novel anticancer treatment research. Up to date, there are no published results in vivo on anticancer effects of certain combinations of non-oncological pleiotropic drugs (disulfiram, metformin, deoxycholic acid, mebendazole) that influence MAPK/PI3K/AKT/mTOR/NF-B signaling. Methods The anticancer effects of certain aforementioned repurposed drugs combinations, <50 % LD50 (equivalent to usual human dose) were assessed by fibrosarcoma growth kinetics (measured daily in vivo by calipers) and tumor proliferation (Ki-67, PCNA), neoangiogenesis (CD34, CD31), glucose metabolism (GLUT1), NO metabolism (iNOS) and apoptosis (COX4, Cytochrome C) in hamsters, randomly allocated to control and experimental groups (6 animals per group). Animals were sacrificed 19 days after BHK-21/C13 tumor inoculation. Tumors were excised, measured and blood collected. Biophysical, pathohistological, toxicological, hematological and biochemical analyses were performed. Results Disulfiram with metformin, disulfiram with deoxycholic acid and deoxycholic acid with metformin are the combinations that have shown significant antitumor effects on the fibrosarcoma growth kinetics and tumor immunohistochemical markers in hamsters (P<0.05). All used drugs in efficacious combinations can inhibit MAPK/PI3K/AKT/mTOR/NF-B signaling. Addition of NF-B stimulator mebendazole to effective two-drug combinations rescued cancer growth, indicating that these pathways may be responsible for antitumor action. Conclusion Combinations of non-oncological drugs: disulfiram with metformin, disulfiram with deoxycholic acid and deoxycholic acid with metformin have the potential to be used as effective non-toxic adjuvant anticancer therapy in oncology.

Jezik

engleski

Datum

2024

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC 4.0 - Creative Commons Autorstvo - Nekomercijalno 4.0 International License.

http://creativecommons.org/licenses/by-nc/4.0/legalcode

Predmet

Keywords: disulfiram, deoxycholic acid, metformin, hamsters, BHK-21/C13, fibrosarcoma

Deo kolekcije (1)

o:28516

Radovi nastavnika i saradnika Državnog univerziteta u Novom Pazaru