The Effectiveness of Endurance Training and Nano Curcumin Supplementation on the Expression of Mir-21and P53 Genes in Brain Tumor Tissue in an Animal Model of Glioblastoma Multiform

Document Type : Research Paper

Authors

1 PhD Student, Department of Exercise Physiology, Borujerd Branch, Islamic Azad University, Borujerd, Iran.

2 Associate Professor of Exercise Physiology Education &Sport Sciences, East Tehran Branch, Islamic Azad University, Tehran, Iran.

3 Assistant Professor, Department of Motor Behavior, Borujerd Branch, Islamic Azad University, Borujerd, Iran.

4 Assistant Professor of Sports Physiology-Cardiovascular and Respiratory, Department of Sports Science, Jahrom University, Jahrom, Iran.

5 Associate Professor of Sports Physiology Research Center, Lifestyle Research Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Abstract

Introduction: Glioblastoma multiforme is the foremost common harmful tumor of the central nervous system that specifically influences the brain and is resistent to common therapies such as surgery, radiotherapy and chemotherapy. The aim of this study was to examine the viability of perseverance preparing and Nano-curcumin supplementation on the expression of miR-21 and P53 qualities in brain tumor tissue in a creature demonstrate of glioblastoma multiforme. Methods: In this experiment, 35 8-week-old male Wistar rats were divided into seven groups with 5 rats each: healthy control group, 4-week-old healthy, control group cancer, 4-week-old cancer group and training group, Nano-curcumin group and training-Nano-curcumin group. Cancer cells were injected into the right frontal cortex of mice using a pump at a depth of 2.5 mm. One week later, mice entered the treadmill training program (4 weeks) and Nano-curcumin was administered orally at a dose of 80 mg/kg (28 days). Gene expression was measured using real-time fluorescent quantitative PCR and used for analysis.spss software. Results: The expression of miR-21 gene in the training group, Nano-curcumin, and training group Nano-curcumin was lower than that of the control cancer at 4 weeks (P = 0.001). Moreover, the expression of P53 gene in the Nano-curcumin training group and Nano-curcumin training group was higher in cancer cells and 4-week blood-eating cancer than in the control group (P = 0.001). Conclusion: Endurance training and curcumin administration appear to reduce tumor growth in mice with brain tumors by modulating the expression of miR-21 and p53 genes.

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  1. 1.Miyai M, Iwama T, Hara A, Tomita H. Exploring the Vital Link Between Glioma, Neuron, and Neural Activity in the Context of Invasion. The American Journal of Pathology. 2023; 193(6):669-79.

    2.Qiu W, Guo Q, Guo X, Wang C, Li B, Qi Y, Wang S, Zhao R, Han X, Du H, Zhao S. Mesenchymal stem cells, as glioma exosomal immunosuppressive signal multipliers, enhance MDSCs immunosuppressive activity through the miR-21/SP1/DNMT1 positive feedback loop. Journal of Nanobiotechnology. 2023; 21(1):1-9.

    1. Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, Ghaffari SH. An overview of microRNAs: biology, functions, therapeutics, and analysis methods. Journal of cellular physiology. 2019; 234 (5):5451-65. (Persian)
    2. Soltani R, Gaeini A, Nuri R. The effects of 8 weeks aerobic training on HIF-1α, miR-21 and VEGF gene expression in female Balb/c with breast cancer. Yafteh. 2019; 21(1):63-74. (Persian)
    3. Ma X, Choudhury SN, Hua X, Dai Z, Li Y. Interaction of the oncogenic miR-21 microRNA and the p53 tumor suppressor pathway. Carcinogenesis. 2013; 34(6):1216-23.
    4. Akbarpour M, Fahollahi F, Muradpourian MR. Effect of Eight Weeks of Aerobic Exercise and Pomegranate Juice Consumption on miR-155, miR-21 and P53 in Men With Prostate Cancer. Complementary Medicine Journal. 2022; 12(1):70-83. (Persian)
    5. Zhou X, Ren Y, Moore L, Mei M, You Y, Xu P, et al. Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status. Laboratory investigation. 2010; 90(2):144-55.
    6. Azarhoush R SS, Besharat S, Meftah N, Rabiei M, Roushandel G, et al. Study of The P53 gene expression by immunohistochemistry in patients with gastric cancer at 5th azar hospital in gorgan, iran. Journal of Sabzevar University of Medical Sciences 2006; 13:74-9. (Persian)
    7. Lago CU, Sung HJ, Ma W, Wang PY, Hwang PM. p53, aerobic metabolism, and cancer. Antioxidants & Redox Signaling. 2011; 15(6): 1739-48.
    8. Pourjafarian J, Kandi M. The effect of endurance training with nano-curcumin supplementation on p53-p21 axis and TERF2 gene expression in muscle tissue of male wistar rats: an experimental study. Journal of Rafsanjan University of Medical Sciences. 2023; 21(11):1103-14. (Persian)
    9. Steigerwalt R, Nebbioso M, Appendino G, Belcaro G, Ciammaichella G, Cornelli U, et al. Meriva®, a lecithinized curcumin delivery system, in diabetic microangiopathy and retinopathy. Panminerva Medica. 2012; 54(4):11.
    10. Layos L, Martínez-Balibrea E, Ruiz de Porras V. Curcumin: a novel way to improve quality of life for colorectal cancer patients?. International Journal of Molecular Sciences. 2022; 23(22):14058
    11. Lin JK. Molecular targets of curcumin. The molecular targets and therapeutic uses of curcumin in health and disease. AEMB. 2007; 595: 227-43.

    14.Varalakshmi Ch, Ali AM, Pardhasaradhi BV, Srivastava RM, Singh S, Khar A. Immunomodulatory effects of curcumin: In-vivo. Int Immunopharmacol. 2008; 8(5): 688-700.

    1. Rouhi L. Apoptosis induction and enhanced expression of p53 and PARP genes in the human anaplastic thyroid carcinoma cells line (SW-1736) with Curcumin. SSU_Journals. 2018; 26(9):759-6. (Persian)
    2. Wang X, Hang Y, Liu J, Hou Y, Wang N, Wang M. Anticancer effect of curcumin inhibits cell growth through miR-21/PTEN/Akt pathway in breast cancer cell. Oncology Letters. 2017; 13(6):4825-31.
    3. Westerlind KC. Physical activity and cancer prevention—mechanisms. Medicine & Science in Sports & Exercise. 2003; 35(11):1834-40.
    4. Jia N, Zhou Y, Dong X, Ding M. The antitumor mechanisms of aerobic exercise: A review of recent preclinical studies. J Cancer Medicine 2021; 10(18): 6365-73.‏
    5. Barnard RJ, Leung PS, Aronson WJ, Cohen P, Golding LA. A mechanism to explain how regular exercise might reduce the risk for clinical prostate cancer. European Journal of Cancer Prevention. 2007; 16(5):415-21.
    6. Zlotogorski A, Dayan A, Dayan D, Chaushu G, Salo T, Vered M. Nutraceuticals as new treatment approaches for oral cancer–I: Curcumin. Oral oncology. 2013; 49(3):187-91.
    7. Roy S, Yu Y, Padhye SB, Sarkar FH, Majumdar AP. Difluorinated-curcumin (CDF) restores PTEN expression in colon cancer cells by down-regulating miR-21. PLoS One. 2013; 8(7):e68543.
    8. Vijayakurup V, Thulasidasan AT, Shankar G M, Retnakumari AP, Nandan CD, Somaraj J, et al. Chitosan encapsulation enhances the bioavailability and tissue retention of curcumin and improves its efficacy in preventing B [a] P-induced lung carcinogenesis. Cancer Prevention Research. 2019; 12(4): 225-36.
    9. Al-Jarrah M, Matalka I, Al Aseri H, Mohtaseb A, Smirnova IV, Novikova L, et al. Exercise training prevents endometrial hyperplasia and biomarkers for endometrial cancer in rat model of type 1 diabetes. Journal of Clinical Medicine Research. 2010; 2(5):207.
    10. Zanotto-Filho A, Braganhol E, Edelweiss MI, Behr GA, Zanin R, Schröder R, et al. The curry spice curcumin selectively inhibits cancer cells growth in vitro and in preclinical model of glioblastoma. The Journal of Nutritional Biochemistry. 2012; 23(6): 591-601.
    11. Swanson LW. Brain maps 4.0—Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps. Journal of Comparative Neurology. 2018; 526(6):935-43.
    12. Betof AS, Dewhirst MW, Jones LW. Effects and potential mechanisms of exercise training on cancer progression: a translational perspective. Brain, Behavior, and Immunity. 2013; 30: 75-87.
    13. DelfanM, Rasekh Nejad Z, Delphan M. Synergistic Effect of Endurance Training Combined with Curcumin on Intratumoral Expression of Interleukin-4 (Il4) and Stat-6 in Female Mice with Breast Cancer. Iranian Quarterly Journal of Breast Disease. 2020; 13(3): 52-61. (Persian)
    14. Parvareh G, Talebi-Garakani E, Shirvani H. Exercise training and nanocurcumin induce down-regulation of EGFR/MAPK/STAT5/FN14 pathway genes in tumor tissue of glioblastoma multiform model rats. Annals of Military and Health Sciences Research. 2022; 20(4). (Persian)
    15. Toufighi A, Agha Alinezhad H, Mohammad Hasan Z, Keyvani F, Ghasemi A. Effect of continuous aerobic exercise on the rate of IL-4, INF-& and proportion of CD4 in mice with breast cancer tumor. Olympic. 2010; 17(4):73-82. (Persian)
    16. Hosseinimehr SJ. A review of preventive and therapeutic effects of curcumin in patients with cancer. J Clin Excell. 2014; 2(2):13. (Persian)
    17. Nazari R, Sattarahmady N, Heli H. Nano-technological methods for increasing the oral bioavailability of curcumin. Journal of Advanced Biomedical Sciences. 2017; 7(2):152-61. (Persian)
    18. Dufresne S, Rébillard A, Muti P, Friedenreich CM, Brenner DR. A review of physical activity and circulating miRNA expression: implications in cancer risk and progression. Cancer Epidemiology, Biomarkers & Prevention. 2018; 27(1):11-24.
    19. Amani-Shalamzari S, Agha Alinejad H, Shahbazi S, Alizadeh S. The effect of endurance training on expression of miR-21 and its downstream in breast cancer bearing mice. Journal of Basic Research in Medical Sciences. 2020; 7(2): 47-57. (Persian)
    20. Esmatabadi MJ, Farhangi B, Montazeri M, Monfared H, Sistani RN, Sadeghizadeh M. Up-regulation of miR-21 decreases chemotherapeutic effect of dendrosomal curcumin in breast cancer cells. Iranian journal of basic medical sciences. 2017; 20(4): 350. (Persian)
    21. Ju Q, Zhao L, Gao J, Zhou L, Xu Y, Sun Y, et.al. Mutant p53 increases exosome-mediated transfer of miR-21-3p and miR-769-3p to promote pulmonary metastasis. Chinese Journal of Cancer Research. 2019; 31(3):533.
    22. Baggish AL, Park J, Min PK, Isaacs S, Parker BA, Thompson PD, et al. Rapid upregulation and clearance of distinct circulating microRNAs after prolonged aerobic exercise. Journal of Applied Physiology. 2014; 116(5): 522-31.
    23. Akbari A, Sedaghat M, Heshmati J, Tabaeian SP, Dehghani S, Pizarro AB, et al . Molecular mechanisms underlying curcumin-mediated microRNA regulation in carcinogenesis; Focused on gastrointestinal cancers. Biomedicine & Pharmacotherapy. 2021; 141: 111849. (Persian).
    24. PLOS ONE Editors. Retraction: anti-tumor activity of a novel compound-CDF is mediated by regulating miR-21, miR-200, and PTEN in pancreatic cancer. Public Library of Science San Francisco, CA USA; 2018.
    25. Majidi A, Poozesh Jadidi R, Nourazar MA, Bashiri J, Azali Alamdari K. Effects of Aerobic Training and Curcumin Supplementation on Cardiomyocyte Apoptosis and MiRNAs Expression in Rats Exposed to Arsenic. Sport Physiology. 2020; 12(48): 39-60. (Persian)
    26. Alabaf Yousefi F, Pouzesh Jadidi R, Bashiri J, Azali Alamdari K, Vakili J. The effects of HIIT and curcumin supplementation on CD31+ capillary cell count and the expression of VEGF and MMP9 of left ventricle in isoproterenol induced myocardial infraction model rats. Journal of Sport Biosciences. 2021; 13(2): 179-94. (Persian)
    27. Asghari Rakabardkolaee M, Barari AR, Abdi A, Hasrak K. The review of short-term concurrent training on expression of P53 and P21 tumor suppressor genes in men with prostate cancer. Journal of Knowledge & Health Shahroud University of Medical Sciences. 2018; 13(1). (Persian)
    28. Nakayama M, Sakai E, Echizen K, Yamada Y, Oshima H, Han TS, et al. Intestinal cancer progression by mutant p53 through the acquisition of invasiveness associated with complex glandular formation. Oncogene. 2017; 36(42): 5885-96.
    29. Wang PY, Zhuang J, Hwang PM. P53: exercise capacity and metabolism. Current Opinion in Oncology. 2012; 24(1):76.