Potential anti-tumor activity of kefir-induced juglone and resveratrol fractions against Ehrlich ascites carcinoma-bearing BALB/c mice

Document Type: Research article

Authors

1 Department of Internal Medicine, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200, Afyonkarahisar, Turkey.

2 Department of Anatomy, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200, Afyonkarahisar, Turkey.

3 Department of Hematology, Faculty of Medicine, Mugla Sitki Kocman University, 48000, Muğla, Turkey.

4 Department of Emergency Medicine, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200, Afyonkarahisar, Turkey.

5 Department of Medical Biochemistry, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200, Afyonkarahisar, Turkey.

6 Department of Chemistry, Faculty of Arts and Sciences, Yildiz Technical University, 34220, Istanbul, Turkey.

7 Department of Biology, Faculty of Science, Karamanoglu Mehmetbey University, 70100, Karaman, Turkey.

8 Department of Histology, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200, Afyonkarahisar, Turkey.

9 Department of Biochemistry, Faculty of Medicine, Karabük University, 78020, Karabük, Turkey.

10 Department of Medical Pharmacology, Faculty of Medicine, Afyonkarahisar Health Sciences University, 03200, Afyonkarahisar, Turkey.

Abstract

We investigated the potential influence of kefir-induced juglone and resveratrol fractions (JRK) against Ehrlich Ascites Carcinoma (EAC) bearing BALB/c male mice. Kefir yeast was grown in the cell culture supplemented with juglone and resveratrol (1:2). After 48 hours incubation, JRK solution was applied (0.1 ml/day i.p.) to the EAC-bearing mice throughout five days. Molecular regulatory mechanisms of apoptotic and anti-apoptotic pathway components were evaluated in the plasma of mice and isolated EAC cells with ELISA, qRT-PCR and immunocytchemical experiments. EAC-induced upregulation in Bcl-2 and downregulation in Caspase-3 were normalized with JRK in the plasma of mice. Additionally, JRK upregulated the expression levels of apoptotic Bax, p53, Caspase-3,8,9, and APAF-1 proteins together with BAX, CASPASE-8, and CASPASE-9 genes in isolated EAC cells. These changes were also associated with decreased expression levels of anti-apoptotic Bcl-2 and Bcl-xl proteins. Immunocytochemical studies also confirmed the activation of apoptotic pathways and repression of anti-apoptotic proteins in EAC cells with JRK treatment. JRK activates apoptotic pathway and inhibits anti-apoptotic genes and proteins in Ehrlich ascites carcinoma- bearing BALB/c mice that could be benefical in cancer treatment.

Graphical Abstract

Potential anti-tumor activity of kefir-induced juglone and resveratrol fractions against Ehrlich ascites carcinoma-bearing BALB/c mice

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