Zingerone improves the immune responses in an animal model of breast cancer
-
Modje Kazemi
, Maryam Nemati
Abstract
Objectives
The potent anti-tumorigenic effects were attributed to ginger and there are some reports regarding the anti-cancer and immunomodulatory properties ginger-derived components. This study aimed to investigate the effects of zingerone on some immune-related parameters in an animal model of breast cancer.
Methods
The breast cancer was established in female BALB/c mice using a carcinogenic 4T1 cell line. At day 10 after cancer induction, tumor-bearing mice were divided into five groups and treated intraperitoneal (daily from days 11–30) with saline or zingerone (at doses 10, 20, 50 and 100 mg/kg/day). The mice were sacrificed on day 31 and the number of splenic Th1- and Treg cells, the expression of IFN-γ and TGF-β in the blood mononuclear cells, the antibody production against sheep red blood cell (SRBC) were determined using flow cytometry, real time-PCR and a standard hemagglutination assay, respectively.
Results
Zingerone at doses 50 and 100 mg/kg enhanced the number of splenic Th1 cells (p<0.03 and 0.007, respectively); at doses 10, 20, 50 and 100 mg/kg reduced the number of splenic Treg cells (p<0.02, 0.01, and 0.01, respectively), at doses 50 and 100 mg/kg enhanced the expression of IFN-γ (p<0.03), at doses 50 and 100 mg/kg reduced the expression of TGF-β, at doses 50 mg/kg reduced the titer of anti-SRBC antibody (p<0.05).
Conclusions
Zingerone improve the T cell-mediated and antibody responses in a mouse model of breast cancer. The immunotherapeutic potentials of zingerone in cancers need more considerations.
Funding source: Kerman University of Medical Sciences
Award Identifier / Grant number: 97000410
Research funding: This research was supported by a grant [NO: 97000410] from the Kerman University of Medical Sciences, Kerman, Iran.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Competing interests: No funding organizations played a role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Ethical statement: A local ethic committee affiliated to Kerman University of Medical Sciences also approved the investigation protocol and the ethic approval cod is IR.KMU.REC.1397.405.
References
1. Godone, RLN, Leitao, GM, Araujo, NB, Castelletti, CHM, Lima-Filho, JL, Martins, DBG. Clinical and molecular aspects of breast cancer: targets and therapies. Biomed Pharmacother 2018;106:14–34. https://doi.org/10.1016/j.biopha.2018.06.066.Search in Google Scholar
2. Li, Z, Song, W, Rubinstein, M, Liu, D. Recent updates in cancer immunotherapy: a comprehensive review and perspective of the 2018 China Cancer Immunotherapy Workshop in Beijing. J Hematol Oncol 2018;11:142. https://doi.org/10.1186/s13045-018-0684-3.Search in Google Scholar
3. Perez-Herrero, E, Fernandez-Medarde, A. Advanced targeted therapies in cancer: drug nanocarriers, the future of chemotherapy. Eur J Pharm Biopharm 2015;93:52–79. https://doi.org/10.1016/j.ejpb.2015.03.018.Search in Google Scholar
4. Mortara, L, Balza, E, Bruno, A, Poggi, A, Orecchia, P, Carnemolla, B. Anti-cancer therapies employing IL-2 cytokine tumor targeting: contribution of innate, adaptive and immunosuppressive cells in the anti-tumor efficacy. Front Immunol 2018;9:2905. https://doi.org/10.3389/fimmu.2018.02905.Search in Google Scholar
5. Chen, X, Wang, J, Wang, R, Su, Q, Luan, J, Huang, H, et al.. Th1-, Th2-, and Th17-associated cytokine expression in hypopharyngeal carcinoma and clinical significance. Eur Arch Oto-Rhino-Laryngol 2016;273:431–8. https://doi.org/10.1007/s00405-015-3779-2.Search in Google Scholar
6. Khalife, E, Khodadadi, A, Talaeizadeh, A, Rahimian, L, Nemati, M, Jafarzadeh, A. Overexpression of regulatory T cell-related markers (FOXP3, CTLA-4 and GITR) by peripheral blood mononuclear cells from patients with breast cancer. Asian Pac J Cancer Prev 2018;19:3019–25. https://doi.org/10.31557/apjcp.2018.19.11.3019.Search in Google Scholar
7. Chatrabnous, N, Ghaderi, A, Ariafar, A, Razeghinia, MS, Nemati, M, Jafarzadeh, A. Serum concentration of interleukin-35 and its association with tumor stages and FOXP3 gene polymorphism in patients with prostate cancer. Cytokine 2019;113:221–7. https://doi.org/10.1016/j.cyto.2018.07.006.Search in Google Scholar
8. Jafarzadeh, A, Mohammadi-Kordkhayli, M, Ahangar-Parvin, R, Azizi, V, Khoramdel-Azad, H, Shamsizadeh, A, et al.. Ginger extracts influence the expression of IL-27 and IL-33 in the central nervous system in experimental autoimmune encephalomyelitis and ameliorates the clinical symptoms of disease. J Neuroimmunol 2014;276:80–8. https://doi.org/10.1016/j.jneuroim.2014.08.614.Search in Google Scholar
9. Jafarzadeh, A, Nemati, M. Therapeutic potentials of ginger for treatment of multiple sclerosis: a review with emphasis on its immunomodulatory, anti-inflammatory and anti-oxidative properties. J Neuroimmunol 2018;324:54–75. https://doi.org/10.1016/j.jneuroim.2018.09.003.Search in Google Scholar
10. Choi, JG, Kim, SY, Jeong, M, Oh, MS. Pharmacotherapeutic potential of ginger and its compounds in age-related neurological disorders. Pharmacol Ther 2018;182:56–69. https://doi.org/10.1016/j.pharmthera.2017.08.010.Search in Google Scholar
11. de Lima, RMT, Dos Reis, AC, de Menezes, APM, Santos, JVO, Filho, J, Ferreira, JRO, et al.. Protective and therapeutic potential of ginger (Zingiber officinale) extract and [6]-gingerol in cancer: a comprehensive review. Phytother Res 2018;32:1885–907. https://doi.org/10.1002/ptr.6134.Search in Google Scholar
12. Ahmad, B, Rehman, MU, Amin, I, Arif, A, Rasool, S, Bhat, SA, et al.. A review on pharmacological properties of zingerone (4-(4-hydroxy-3-methoxyphenyl)-2-butanone). Sci World J 2015;2015:816364. https://doi.org/10.1155/2015/816364.Search in Google Scholar
13. Yazdi, MH, Mahdavi, M, Faghfuri, E, Faramarzi, MA, Sepehrizadeh, Z, Hassan, ZM, et al.. Th1 immune response induction by biogenic selenium nanoparticles in mice with breast cancer: preliminary vaccine model. Iran J Biotechnol 2015;13:1–9. https://doi.org/10.15171/ijb.1056.Search in Google Scholar
14. Jafarzadeh, A, Bakhshi, H, Rezayati, MT, Nemati, M. Cigarette smoke-exposed saliva suppresses cellular and humoral immune responses in an animal model. J Pakistan Med Assoc 2009;59:760–3.Search in Google Scholar
15. Choi, J-S, Ryu, J, Bae, W-Y, Park, A, Nam, S, Kim, J-E, et al.. Zingerone suppresses tumor development through decreasing cyclin D1 expression and inducing mitotic arrest. Int J Mol Sci 2018;19:2832. https://doi.org/10.3390/ijms19092832.Search in Google Scholar
16. Bae, WY, Choi, JS, Kim, JE, Park, C, Jeong, JW. Zingerone suppresses angiogenesis via inhibition of matrix metalloproteinases during tumor development. Oncotarget 2016;7:47232. https://doi.org/10.18632/oncotarget.10030.Search in Google Scholar
17. Kung, M-L, Lin, P-Y, Huang, S-T, Tai, M-H, Hsieh, S-L, Wu, C-C, et al.. Zingerone nanotetramer strengthened the polypharmacological efficacy of zingerone on human hepatoma cell lines. ACS Appl Mater Interfaces 2018;11:137–50. https://doi.org/10.1021/acsami.8b14559.Search in Google Scholar
18. Ganaie, MA, Al Saeedan, A, Madhkali, H, Jan, BL, Khatlani, T, Sheikh, IA, et al.. Chemopreventive efficacy zingerone (4-[4-hydroxy-3-methylphenyl] butan-2-one) in experimental colon carcinogenesis in Wistar rats. Environ Toxicol 2019;34:610–25. https://doi.org/10.1002/tox.22727.Search in Google Scholar
19. Chraa, D, Naim, A, Olive, D, Badou, A. T lymphocyte subsets in cancer immunity: friends or foes. J Leukoc Biol 2019;105:243–55. https://doi.org/10.1002/jlb.mr0318-097r.Search in Google Scholar
20. Slattery, ML, Lundgreen, A, Bondurant, KL, Wolff, RK. Interferon-signaling pathway: associations with colon and rectal cancer risk and subsequent survival. Carcinogenesis 2011;32:1660–7. https://doi.org/10.1093/carcin/bgr189.Search in Google Scholar
21. Sheikhi, A, Jafarzadeh, A, Kokhaei, P, Hojjat-Farsangi, M. Whole tumor cell vaccine adjuvants: comparing IL-12 to IL-2 and IL-15. Iran J Immunol 2016;13:148–66.Search in Google Scholar
22. Wing, JB, Tanaka, A, Sakaguchi, S. Human FOXP3(+) regulatory T cell heterogeneity and function in autoimmunity and cancer. Immunity 2019;50:302–16. https://doi.org/10.1016/j.immuni.2019.01.020.Search in Google Scholar
23. Sarvaria, A, Madrigal, JA, Saudemont, A. B cell regulation in cancer and anti-tumor immunity. Cell Mol Immunol 2017;14:662–74. https://doi.org/10.1038/cmi.2017.35.Search in Google Scholar
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Reviews
- The effect of Nigella sativa on oxidative stress and inflammatory biomarkers: a systematic review and meta-analysis
- Effect of fennel on primary dysmenorrhea: a systematic review and meta-analysis
- Raising burden of non-communicable diseases: importance of integrating Yoga and Naturopathy at primary care level
- Research Articles Basic
- Marketing and legal status of phytomedicines and food supplements in Morocco
- Hydrogen sulfide as a mediator of endothelium-dependent relaxation evoked by Moringa oleifera leaf extract in mesenteric arterial beds isolated from L-NAME hypertensive rats
- Acute and sub-acute toxicity assessment of aqueous leaves extract of Crassocephalum crepidioides (Asteraceae) in Wistar rats
- Zingerone improves the immune responses in an animal model of breast cancer
- Evaluation of efficacy of Bombax ceiba extract and its major constituent, mangiferin in streptozotocin (STZ)-induced diabetic rats
- Bacterial endosymbiont inhabiting Leucaena leucocephala leaves and their antioxidant and antidiabetic potential
- Ameliorative effect of morin on dutasteride-tamsulosin-induced testicular oxidative stress in rat
- The potentiation of beta-lactam and anti-bacterial activities of lipophilic constituents from Mesua ferrae leaves against methicillin-resistant Staphylococcus aureus
- Influence of irisin on diet-induced metabolic syndrome in experimental rat model
- Modulatory effect of methanol extract of Annona muricata stem bark on mitochondrial membrane permeability transition pore in normal rat liver and monosodium glutamate-induced uterine hyperplasia
- Research Articles Clinical
- Functional status in adhesive capsulitis – yoga vs. physiotherapy: a quasi experimental study
- Okada Purifying Therapy in combination with duloxetine vs. duloxetine alone in patients with TMD and fibromyalgia: a randomized clinical study
- The FIFA 11+ does not alter performance in amateur female basketball players—a randomized control trial
- Body composition, phenotype and central obesity indices in Egyptian women with non-alcoholic fatty liver disease
- Immediate effect of interscapular cupping on blood pressure, oxygen saturation, pulse rate and chest expansion in sedentary smoker students
- The effects of an olive-oil massage on hemodialysis patients suffering from fatigue at a hemodialysis unit in southern India – a randomized controlled trial
- Effects of epigallocatechin-3-gallate of Camellia sinensis leaves on blood pressure, lipid profile, atherogenic index of plasma and some inflammatory and antioxidant markers in type 2 diabetes mellitus patients: a clinical trial
- The effect of practicing yoga during pregnancy on labor stages length, anxiety and pain: a randomized controlled trial
- Effect of lumbar stabilization exercises and thoracic mobilization with strengthening exercises on pain level, thoracic kyphosis, and functional disability in chronic low back pain
- A prospective controlled study on Ramadan fasting in the healthy young males in summer in Germany: effect on cytokines
- Tualang honey versus steroid impregnated nasal dressing following endoscopic sinus surgery: a randomized controlled trial
- Short Communications
- Improved anti-arthritic activity of ginger extract, a traditional medicine, using novel drug delivery approach
- Efficacy of fenugreek seed extract on men's psychological and physical health: a randomized placebo-controlled double-blind clinical trial
Articles in the same Issue
- Frontmatter
- Reviews
- The effect of Nigella sativa on oxidative stress and inflammatory biomarkers: a systematic review and meta-analysis
- Effect of fennel on primary dysmenorrhea: a systematic review and meta-analysis
- Raising burden of non-communicable diseases: importance of integrating Yoga and Naturopathy at primary care level
- Research Articles Basic
- Marketing and legal status of phytomedicines and food supplements in Morocco
- Hydrogen sulfide as a mediator of endothelium-dependent relaxation evoked by Moringa oleifera leaf extract in mesenteric arterial beds isolated from L-NAME hypertensive rats
- Acute and sub-acute toxicity assessment of aqueous leaves extract of Crassocephalum crepidioides (Asteraceae) in Wistar rats
- Zingerone improves the immune responses in an animal model of breast cancer
- Evaluation of efficacy of Bombax ceiba extract and its major constituent, mangiferin in streptozotocin (STZ)-induced diabetic rats
- Bacterial endosymbiont inhabiting Leucaena leucocephala leaves and their antioxidant and antidiabetic potential
- Ameliorative effect of morin on dutasteride-tamsulosin-induced testicular oxidative stress in rat
- The potentiation of beta-lactam and anti-bacterial activities of lipophilic constituents from Mesua ferrae leaves against methicillin-resistant Staphylococcus aureus
- Influence of irisin on diet-induced metabolic syndrome in experimental rat model
- Modulatory effect of methanol extract of Annona muricata stem bark on mitochondrial membrane permeability transition pore in normal rat liver and monosodium glutamate-induced uterine hyperplasia
- Research Articles Clinical
- Functional status in adhesive capsulitis – yoga vs. physiotherapy: a quasi experimental study
- Okada Purifying Therapy in combination with duloxetine vs. duloxetine alone in patients with TMD and fibromyalgia: a randomized clinical study
- The FIFA 11+ does not alter performance in amateur female basketball players—a randomized control trial
- Body composition, phenotype and central obesity indices in Egyptian women with non-alcoholic fatty liver disease
- Immediate effect of interscapular cupping on blood pressure, oxygen saturation, pulse rate and chest expansion in sedentary smoker students
- The effects of an olive-oil massage on hemodialysis patients suffering from fatigue at a hemodialysis unit in southern India – a randomized controlled trial
- Effects of epigallocatechin-3-gallate of Camellia sinensis leaves on blood pressure, lipid profile, atherogenic index of plasma and some inflammatory and antioxidant markers in type 2 diabetes mellitus patients: a clinical trial
- The effect of practicing yoga during pregnancy on labor stages length, anxiety and pain: a randomized controlled trial
- Effect of lumbar stabilization exercises and thoracic mobilization with strengthening exercises on pain level, thoracic kyphosis, and functional disability in chronic low back pain
- A prospective controlled study on Ramadan fasting in the healthy young males in summer in Germany: effect on cytokines
- Tualang honey versus steroid impregnated nasal dressing following endoscopic sinus surgery: a randomized controlled trial
- Short Communications
- Improved anti-arthritic activity of ginger extract, a traditional medicine, using novel drug delivery approach
- Efficacy of fenugreek seed extract on men's psychological and physical health: a randomized placebo-controlled double-blind clinical trial