Immunohistochemical evidences of anticancer actions of metformin with other repurposed drug combinations and correlation with hamster fibrosarcoma tumor size

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Published: Apr 26, 2024
Updated: 26.04.2024
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26.04.2024 (2)
DOI: https://doi.org/10.2298/JSC231203007P
Keywords:
tumor markers fibrosarcoma metformin repurposed drugs hamsters

Main Article Content

Jovan K. Popović
University of Novi Sad, Faculty of Medicine, Department of Pharmacology, Toxicology and Clinical Pharmacology, Novi Sad, Serbia
https://orcid.org/0000-0001-7880-0874
Dušıca J. Popovıć
Department of Biomedical Sciences, State University of Novi Pazar, Vuka Karadžića 9, 36300 Novi Pazar, Serbia
https://orcid.org/0000-0001-7880-0874
Kosta J. Popovıć
Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia
https://orcid.org/0000-0001-7895-9009
Dejan Mıljkovıć
Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia
https://orcid.org/0000-0002-7739-5202
Dušan Laloševıć
Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia
https://orcid.org/0000-0002-0760-9180
Zana Dolićanin
Department of Biomedical Sciences, State University of Novi Pazar, Vuka Karadžića 9, 36300 Novi Pazar, Serbia
https://orcid.org/0000-0003-0457-3087
Ivan Čapo
Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia
https://orcid.org/0000-0001-7531-5099

Abstract

The aim was to detect and correlate anticancer effects of metformin in combinations with other repurposed drugs, already registered for other indications, which may be immediately applied and clinically investigated in oncology, reducing the time and cost of research for new cancer treatments. Immunohistochemistry was performed for tumors treated by dual drug combinations containing metformin with deoxycholic acid, caffeine, itraconazole, nitroglycerin, disulfiram or diclofenac. The drugs were applied in Syrian golden hamsters (6 animals per group) with inoculated BHK21/C13 fibrosarcoma in doses equivalent to usual human doses, <50 % LD50. The anticancer effects were assessed by: p53 (mutational status); Ki-67 and PCNA (tumor proliferation); CD34 and CD31 (neoangiogenesis); GLUT1 (glucose metabolism); iNOS (NO metabolism); COX4, Cytochrome C and caspase 3 (apoptosis); immunohistochemical markers. Also, biophysical characteristics of fibrosarcoma, animal blood samples and the toxicity on main organs were analyzed. Treatments significantly (P<0.05) reduced mutational status, tumor proliferation, neoangiogenesis, glucose metabolism, NO metabolism and modulated apoptosis, in correlation with tumor size, without toxicity and influence on biochemical blood and hematological tests. Administration of metformin in two-drug combination with deoxycholic acid, caffeine, itraconazole, nitroglycerin, disulfiram or diclofenac may be recommended for further clinical investigations in oncology.

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[1]
J. Popović, “Immunohistochemical evidences of anticancer actions of metformin with other repurposed drug combinations and correlation with hamster fibrosarcoma tumor size”, J. Serb. Chem. Soc., Apr. 2024.
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15 years of Professor Emeritus UNS
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Author Biographies

Jovan K. Popović, University of Novi Sad, Faculty of Medicine, Department of Pharmacology, Toxicology and Clinical Pharmacology, Novi Sad, Serbia

Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Dušıca J. Popovıć, Department of Biomedical Sciences, State University of Novi Pazar, Vuka Karadžića 9, 36300 Novi Pazar, Serbia

Department of Biomedical Sciences, State University of Novi Pazar, Novi Pazar, Serbia

Kosta J. Popovıć, Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia

Department of Pharmacy, Faculty of Medicine, University of Novi Sad

Dejan Mıljkovıć, Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia

Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Dušan Laloševıć, Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia

Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Zana Dolićanin, Department of Biomedical Sciences, State University of Novi Pazar, Vuka Karadžića 9, 36300 Novi Pazar, Serbia

Department of Biomedical Sciences, State University of Novi Pazar, Novi Pazar, Serbia

Ivan Čapo, Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia

Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

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