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Naringenin and Cryptotanshinone Shift The Immune Response Towards Th1 and Modulate T Regulatory Cells Via Jak2/Stat3 Pathway in Breast Cancer Publisher Pubmed



Noori S1 ; Nourbakhsh M2, 3 ; Imani H4 ; Deravi N1 ; Salehi N1 ; Abdolvahabi Z5
Authors
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Authors Affiliations
  1. 1. Department of Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Nutrition Department, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Metabolic Diseases Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran

Source: BMC Complementary Medicine and Therapies Published:2022


Abstract

Background: Use of natural products has been proposed as an efficient method in modulation of immune system and treatment of cancers. The aim of this study was to investigate the potential of cryptotanshinone (CPT), naringenin, and their combination in modulating the immune response towards Th1 cells and the involvement of JAK2/STAT3 signaling pathway in these effects. Methods: Mouse models of delayed type hypersensitivity (DTH) were produced and treated with naringenin and CPT. The proliferation of spleen cells were assessed by Bromodeoxyuridine (BrdU) assay. Flowcytometry and enzyme-linked immunosorbent assay (ELISA) tests were employed to evaluate subpopulation of T-lymphocytes and the levels of cytokines, respectively. The JAK/STAT signaling pathway was analyzed by Western blotting. Results: We showed higher DTH, increased lymphocyte proliferation, decreased tumor growth and reduced JAK2/STAT3 phosphorylation in mice treated with naringenin and CPT. Moreover, a significant decline in the production of IL-4 and an upsurge in the production of IFN-γ by splenocytes were observed. Additionally, the population of intra-tumor CD4+CD25+Foxp3+ T cells was significantly lower in naringenin + CPT treated animals than that in controls. Conclusion: Naringenin-CPT combination could exert immunomodulatory effects, suggesting this combination as a novel complementary therapeutic regimen for breast cancer. © 2022, The Author(s).
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