نوع مقاله : مقاله پژوهشی

نویسندگان

1 دکتری فیزیولوژی ورزشی، دانشکدة علوم ورزشی، دانشگاه بیرجند، بیرجند، ایران

2 استاد فیزیولوژی ورزشی، دانشکدة علوم ورزشی، دانشگاه بیرجند، بیرجند، ایران

3 دانشیار بیوشیمی، مرکز تحقیقات سلولی-مولکولی، دانشکدة پزشکی، دانشگاه علوم پزشکی بیرجند، بیرجند، ایران و دانشیار بیوشیمی، گروه میکروبیولوژی و ژنتیک مولکولی، دانشگاه ایالتی میشیگان، آمریکا

4 استاد بیوشیمی، مرکز تحقیقات سلولی مولکولی غدد درون‌ریز، پژوهشکدة علوم غدد درون‌ریز و متابولیسم، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران

5 دانشجوی دکتری فیزیولوژی ورزشی، دانشکدة علوم ورزشی، دانشگاه بیرجند، بیرجند، ایران

چکیده

مطالعات نشان می ­دهند که تمرین ورزشی و ترکیبات فعال زیستی زعفران می ­توانند باعث کاهش آپوپتوز و کاشکسی ناشی از سرطان شوند. پژوهش حاضر با هدف بررسی اثر چهار هفته تمرین تناوبی شدید (HIIT) و مصرف عصارة آبی زعفران (SAE) بر بیان برخی ژن­ های مرتبط با کاشکسی (SIRT1، hTERT و p53) در عضلة دوقلوی موش ­های حامل ردة سلولی 4T1 سرطان پستان انجام شد؛ براین‌اساس، 44 سر موش BALB/c ماده به ­طور تصادفی در گروه ­های تمرین تناوبی شدید (HIIT)، عصارة آبی زعفران (SAE)، تمرین تناوبی شدید + عصارة آبی زعفران (HIIT+SAE)، کنترل و شم قرار گرفتند. پس از 48 ساعت از آخرین جلسة مداخله، عضلة دوقلو با روش جراحی برای آنالیزهای بعدی برداشته شد. نتایج نشان داد بیان ژن SIRT1 در گروه HIIT به‌طور معنا­داری از گروه­ کنترل و HIIT+SAE بالاتر بود (به‌ترتیب 0.03P =  و  0.02P = ). همچنین بیان ژن hTERT در گروه HIIT به­ طور معنا­داری از سایر گروه­های مطالعه‌شده بالاتر بود (P < 0.05) و درگروه SAE به­طور معنا­داری از گروه HIIT+SAE بالاتر بود (P = 0.01). علاوه‌براین، بیان ژن p53 در گروه‌های HIIT و HIIT+SAE به ­طور معنا­داری از گروه SAE پایین‌تر بود (به‌ترتیب 0.003  P = و 0.004P =). براساس نتایج، به‌نظر می­رسد HIIT احتمالاً نقش مثبتی در کاهش اثرات کاشکسی ناشی از سرطان با تنظیم بیان بالاتر ژن‌های SIRT1 و hTERT و بیان پایین ­تر ژن p53 دارد و می ­تواند در کاهش تحلیل عضلات ناشی از سرطان مؤثر باشد.

کلیدواژه‌ها

موضوعات

  1. Mijwel S, Backman M, Bolam KA, Jervaeus A, Sundberg CJ, Margolin S, et al. Adding high-intensity interval training to conventional training modalities: optimizing health-related outcomes during chemotherapy for breast cancer: the OptiTrain randomized controlled trial. Breast Cancer Res Treat. 2018;168(1):79-93.
  2. Narasimhan A, Greiner R, Bathe OF, Baracos V, Damaraju S. Differentially expressed alternatively spliced genes in skeletal muscle from cancer patients with cachexia. J Cachexia Sarcopenia Muscle. 2018;9(1):60-70.
  3. Myers MJ, Shepherd DL, Durr AJ, Stanton DS, Mohamed JS, Hollander JM, et al. The role of SIRT1 in skeletal muscle function and repair of older mice. J Cachexia Sarcopenia Muscle. 2019;10(4):929-49.
  4. Lee D, Goldberg AL. SIRT1 protein, by blocking the activities of transcription factors FoxO1 and FoxO3, inhibits muscle atrophy and promotes muscle growth. J Biol Chem. 2013;288(42):30515-26.
  5. Simão AL, Afonso MB, Rodrigues PM, Gama-Carvalho M, Machado MV, Cortez-Pinto H, et al. Skeletal muscle miR-34a/SIRT1: AMPK axis is activated in experimental and human non-alcoholic steatohepatitis. J Mol Med. 2019;97(8):1113-26.
  6. Cross WL, Roby MA, Deschenes MR, Harris MB. Myocardial SIRT1 expression following endurance and resistance exercise training in young and old rats. The FASEB J. 2008;22(S1):753.1.
  7. Gurd BJ, Perry CGR, Heigenhauser GJF, Spriet LL, Bonen A. High-intensity interval training increases SIRT1 activity in human skeletal muscle. Appl Physiol Nutr Metab. 2010;35(3):350-7.
  8. Crea F, Sarti D, Falciani F, Al-Rubeai M. Over-expression of hTERT in CHO K1 results in decreased apoptosis and reduced serum dependency. J Biotechnol. 2006;121(2):109-23.
  9. Kim W, Ludlow AT, Min J, Robin JD, Stadler G, Mender I, et al. Regulation of the human telomerase gene TERT by telomere position effect—over long distances (TPE-OLD): implications for aging and cancer. PLOS Biol. 2016;14(12):e2000016.
  10. Chilton WL, Marques FZ, West J, Kannourakis G, Berzins SP, O’Brien BJ, et al. Acute exercise leads to regulation of telomere-associated genes and microRNA expression in immune cells. PLOS One. 2014;9(4):e92088.
  11. Cudré-Mauroux C, Occhiodoro T, König S, Salmon P, Bernheim L, Trono D. Lentivector-mediated transfer of bmi-1 and telomerase in muscle satellite cells yields a duchenne myoblast cell line with long-term genotypic and phenotypic stability. Hum Gene Ther. 2003;14(16):1525-33.
  12. Liu Y, Su H, Jiang Z, Wen T, Shao JJEBR. Effect of HIIT on mitochondrial telomerase of skeletal muscle in aged rats. Exercise Biochemistry Review. 2018;1(3):1.  
  13. Levine AJ, Oren M. The first 30 years of p53: growing ever more complex. Nat Rev Cancer. 2009;9:749-58
  14. Morimoto Y, Kureishi Bando Y, Shigeta T, Monji A, Murohara T. Atorvastatin prevents ischemic limb loss in type 2 diabetes: Role of p53. J Atheroscler Thromb. 2010;1011240321.
  15. Qi Z, He J, Zhang Y, Shao Y, Ding S. Exercise training attenuates oxidative stress and decreases p53 protein content in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. Free Radic Biol Med. 2011;50(7):794-800.
  16. Vainshtein A, Kazak L, Hood DA. Effects of endurance training on apoptotic susceptibility in striated muscle. J Appl Physiol. 2011;110(6):1638-45.
  17. Di Girolamo FG, Guadagni M, Fiotti N, Situlin R, Biolo G. Contraction and nutrition interaction promotes anabolism in cachectic muscle. Curr Opin Clin Nutr Metab Care. 2019;22(1):60-7.
  18. Soleymani Z, Peeri M. Comparision the effect of high intensity interval training and continuous endurance training on expression of MYOD in Soleus muscle of diabetic rats. Physiology of Sport and Physical Activity.2016;18:1417-23. (In Persian).
  19. Jung H-W, Kim JW, Kim J-Y, Kim S-W, Yang HK, Lee JW, et al. Effect of muscle mass on toxicity and survival in patients with colon cancer undergoing adjuvant chemotherapy. Support Care Cancer. 2015;23(3):687-94.
  20. Ballarò R, Beltrà M, De Lucia S, Pin F, Ranjbar K, Hulmi JJ, et al. Moderate exercise in mice improves cancer plus chemotherapy-induced muscle wasting and mitochondrial alterations. The FASEB Journal. 2019;33(4):5482-94.
  21. Mugele H, Freitag N, Wilhelmi J, Yang Y, Cheng S, Bloch W, et al. High-intensity interval training in the therapy and aftercare of cancer patients: a systematic review with meta-analysis. J Cancer Surviv. 2019;13(2):205-23.
  22. Ahmadabadi F, Saghebjoo M, Huang CJ, Saffari I, Zardast M. The effects of high-intensity interval training and saffron aqueous extract supplementation on alterations of body weight and apoptotic indices in skeletal muscle of 4T1 breast cancer-bearing mice with cachexia. Appl Physiol Nutr Metab. 2020;45(5):555-63.
  23. Nezamdoost Z, Saghebjoo M, Hoshyar R, Hedayati M, Keska A. High-intensity training and saffron: effects on breast cancer-related gene expression. Med Sci Sport Exer. 2020: 52(7):1470-76.
  24. Buetler TM, Renard M, Offord EA, Schneider H, Ruegg UT. Green tea extract decreases muscle necrosis in mdx mice and protects against reactive oxygen species. Am J Clin Nutr. 2002;75(4):749-53.
  25. Velázquez KT, Enos RT, Narsale AA, Puppa MJ, Davis JM, Murphy EA, et al. Quercetin supplementation attenuates the progression of cancer cachexia in cpcMin/+mice. J Nutr. 2014;144(6):868-75.
  26. Ábrigo J, Elorza AA, Riedel CA, Vilos C, Simon F, Cabrera D, et al. Role of oxidative stress as key regulator of muscle wasting during cachexia. Oxid Med Cell Longev. 2018;2018:2063179.
  27. Moradzadeh M, Kalani MR, Avan A. The antileukemic effects of saffron (Crocus sativus L.) and its related molecular targets: A mini review. J Cell Biochem. 2019;120(4):4732-8.
  28. Arzi L, Farahi A, Jafarzadeh N, Riazi G, Sadeghizadeh M, Hoshyar R. Inhibitory effect of crocin on metastasis of triple-negative breast cancer by interfering with wnt/β-catenin pathway in murine model. DNA Cell Biol. 2018;37(12):1068-75.
  29. Jensen MM, Jørgensen JT, Binderup T, Kjær A. Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18FFDG-microPET or external caliper. BMC Med Imaging. 2008;8(1):1-9.
  30. Delphan M, Agha Alinejad H, Delfan M, Dehghan S. Intratumoral effects of continuous endurance training and high intensity interval training on genes expression of miR-21 and bcl-2 in breast cancer bearing female mice Iran. J Breast Dis. 2017;10(2):49-57.
  31. Marcinko K, Sikkema SR, Samaan MC, Kemp BE, Fullerton MD, Steinberg GR. High intensity interval training improves liver and adipose tissue insulin sensitivity. Mol Metab. 2015;4(12):903-15.
  32. Moallem SA, Afshar M, Etemad L, Razavi BM, Hosseinzadeh H. Evaluation of teratogenic effects of crocin and safranal, active ingredients of saffron, in mice. Toxicol Ind Health. 2016 Feb;32(2):285-91.
  33. Bathaie SZ, Hoshyar R, Miri H, Sadeghizadeh MJB, Biology C. Anticancer effects of crocetin in both human adenocarcinoma gastric cancer cells and rat model of gastric cancer. Biochem. Cell Biol. 2013;91(6):397-403.
  34. Montero-Bullon J-F, Melo T, Ferreira R, Padrão AI, Oliveira PA, Domingues MRM, et al. Exercise training counteracts urothelial carcinoma-induced alterations in skeletal muscle mitochondria phospholipidome in an animal model. Sci Rep. 2019;9(1):13423.
  35. Chalkiadaki A, Igarashi M, Nasamu AS, Knezevic J, Guarente L. Muscle-specific SIRT1 gain-of-function increases slow-twitch fibers and ameliorates pathophysiology in a mouse model of duchenne muscular dystrophy. Plos Genet. 2014;10(7):e1004490.
  36. Zschoernig B, Mahlknecht U. SIRTUIN 1: Regulating the regulator. Biochem Biophys Res Commun. 2008;376(2):251-5.
  37. Chen W-K, Tsai Y-L, Shibu MA, Shen C-Y, Chang-Lee SN, Chen R-J, et al. Exercise training augments Sirt1-signaling and attenuates cardiac inflammation in D-galactose induced-aging rats. Aging. 2018;10(12):4166-74.
  38. Huang C-C, Wang T, Tung Y-T, Lin W-T. Effect of exercise training on skeletal muscle SIRT1 and PGC-1α expression levels in rats of different age. Int J Med Sci. 2016;13(4):260-70.
  39. 39. Ghilani A, Kaeni AA, Nouri R. Effect of aerobic exercise training and ozone therapy on TRF2 sequences and TERT gene expressions in the heart tissue of rats with osteoarthritis. Studies in Medical Sciences, 2020;31(3):169-77.( In Persian)
  40. Ludlow AT, Witkowski S, Marshall MR, Wang J, Lima LCJ, Guth LM, et al. Chronic exercise modifies age-related telomere dynamics in a tissue-specific fashion. J Gerontol A Biol Sci Med Sci. 2012;67(9):911-26.
  41. Siu PM, Alway SE. Mitochondria-associated apoptotic signalling in denervated rat skeletal muscle. J Physiol. 2005;565(1):309-23.
  42. Molanouri Shamsi M, Chekachak S, Soudi S, Quinn LS, Ranjbar K, Chenari J, et al. Combined effect of aerobic interval training and selenium nanoparticles on expression of IL-15 and IL-10/TNF-α ratio in skeletal muscle of 4T1 breast cancer mice with cachexia. Cytokine. 2017; 90:100-8.
  43. Yanagihara K, Takigahira M, Mihara K, Kubo T, Morimoto C, Morita Y, et al. Inhibitory effects of isoflavones on tumor growth and cachexia in newly established cachectic mouse models carrying human stomach cancers. Nutr Cancer. 2013;65(4):578-89.
  44. Kala R, Shah HN, Martin SL, Tollefsbol TOJBC. Epigenetic-based combinatorial resveratrol and pterostilbene alters DNA damage response by affecting SIRT1 and DNMT enzyme expression, including SIRT1-dependent γ-H2AX and telomerase regulation in triple-negative breast cancer. BMC Cancer. 2015;15(1):672.
  45. Shinozaki S, Chang K, Sakai M, Shimizu N, Yamada M, Tanaka T, et al. Inflammatory stimuli induce inhibitory S-nitrosylation of the deacetylase SIRT1 to increase acetylation and activation of p53 and p65. Sci Signaling. 2014;7(351):ra106.