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

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Published: May 13, 2024
Updated: 13.05.2024
DOI: https://doi.org/10.2298/JSC231203007P
Keywords:
tumor markers fibrosarcoma metformin repurposed drugs hamsters

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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 the 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. The 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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How to Cite
[1]
J. Popović, “Immunohistochemical evidences of anticancer actions of metformin with other repurposed drug combinations and correlation with hamster fibrosarcoma tumor size: Scientific paper”, J. Serb. Chem. Soc., vol. 89, no. 5, pp. 643–656, May 2024.
Issue
Vol. 89 No. 5 (2024): Theme issue honoring 15th anniversary of the election of Professor Emeritus at the University in Novi Sad
Section
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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