The effect of 8 weeks of quercetin supplementation and intermittent exercise on gene expression of Muc5Ac, Muc4 and polyphosphate in rats with colon cancer

Document Type : Research Paper

Authors

1 Department of Sport Sciences, Faculty of Social Sciences, Imam Khomeini International University, Qazvin, Iran.

2 Department of Behavioural and Cognitive Sciences in Sport, Faculty of Sport Science and Health, University of Tehran, Tehran, Iran.

Abstract

Background: Expression of mucosal levels would affect the function of internal organs of the body and the digestive system, such as by creating a blockage for the progression of cancerous tumors and the failure of the target tissue, especially the large intestine.
Aim: The purpose of this sudy was to investigate the effect of 8 weeks of quercetin supplementation and intermittent exercise on protein levels of intestinal Muc5Ac, Muc4 and polyphosphate in rats with colon cancer.
Material and Methods: Tewenty-four rats were randomly assigned into four groups including quercetin (n=6), exercise (n=6), quercetin + exercise (n=6) and control group (n=6). Colon cancer induction was provided with the use of 1,2-dimethylhydrazine for 8 weeks and daily quercetin supplementation of 50 mg/kg body weight of mice by Gavagene method. Exercise protocol was performed 5 sessions per week with intensity of 60-70%, maximum speed of 23 m/min with 2-min rest in 8 weeks. ANOVA was used to analyze data. The level of significance was set at P<0.05.
Results: It was suggested that there was a significant difference in protein levels of intestinal Muc5Ac, Muc4 and polyphosphate in all groups (P<0.05). Furthermore, it was also indicated that Muc5Ac levels was significantly higher in the quercetin+ exercise group other than pther groups (P<0.05).
Conclusions: It was concluded that intermittent exercise and quercetin supplementation would increase the levels of Muc5Ac and Muc4 proteins in the large intestine of mice with colon cancer.  

Keywords


[1] Shirvani H, Bazgir B, Rahimi M, Isanejad A, Samadi M, Sobhani V, et al. "Interval exercise training affects expression of MCT-1, GLUT-1, PFK-1 and p53 as key metabolic regulators on azoxymethane-induced experimental colon cancer". 2021. https://doi.org/10.21203/rs.3.rs-151527/v1.

[2] Terzić J, Grivennikov S, Karin E, Karin M. "Inflammation and colon cancer". Gastroenterology. 2010; 138(6): 2101-14. e5. https://doi.org/10.1053/j.gastro.2010.01.058.   

[3] Arani SH, Kerachian MA. "Rising rates of colorectal cancer among younger Iranians: is diet to blame?". Current Oncology. 2017; 24(2): e131. https://doi.org/10.3747/co.24.3226

[4] Hofseth LJ, Ying L. "Identifying and defusing weapons of mass inflammation in carcinogenesis". Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2006; 1765(1): 74-84. https://doi.org/10.1016/j.bbcan.2005.08.005.   

[5] Itzkowitz SH, Bloom EJ, Kokal WA, Modin G, Hakomori SI, Kim YS. "Sialosyl‐Tn. A novel mucin antigen associated with prognosis in colorectal cancer patients". Cancer. 1990; 66(9): 1960-6. https://doi.org/10.1002/1097-0142(19901101)66:9<1960::AID-CNCR2820660919>3.0.CO;2-X

[6] Forgue‐Lafitte ME, Fabiani B, Levy PP, Maurin N, Fléjou JF, Bara J. "Abnormal expression of M1/MUC5AC mucin in distal colon of patients with diverticulitis, ulcerative colitis and cancer". International Journal of Cancer. 2007; 121(7): 1543-9. https://doi.org/10.1002/ijc.22865

[7] Pothuraju R, Pai P, Chaudhary S, Siddiqui JA, Cox JL, Kaur S, et al. "Depletion of transmembrane mucin 4 (Muc4) alters intestinal homeostasis in a genetically engineered mouse model of colorectal cancer". Aging (Albany NY). 2022; 14(5): 2025. https://doi.org/10.18632/aging.203935.

[8] Moghadamyeghaneh Z, Hanna MH, Hwang G, Mills S, Pigazzi A, Stamos MJ, et al. "Outcomes of colon resection in patients with metastatic colon cancer". The American Journal of Surgery. 2016; 212(2): 264-71. https://doi.org/10.1016/j.amjsurg.2016.01.025

[9] Müller WE, Schröder HC, Neufurth M, Wang X. "An unexpected biomaterial against SARS-CoV-2: Bio-polyphosphate blocks binding of the viral spike to the cell receptor". Materials Today. 2021; 51: 504-524. https://doi.org/10.1016/j.mattod.2021.07.029

[10] Neufurth M, Wang X, Wang S, Schröder HC, Müller WE. "Caged dexamethasone/quercetin nanoparticles, formed of the morphogenetic active inorganic polyphosphate, are strong inducers of MUC5AC". Marine Drugs. 2021; 19(2): 64. https://doi.org/10.3390/md19020064

[11] Trojian TH, Mody K, Chain P. "Exercise and colon cancer: primary and secondary prevention". Current Sports Medicine Reports. 2007; 6(2): 120-4. https://doi.org/10.1097/01.CSMR.0000306452.02069.fa. https://doi.org/10.1007/BF02941153.

[12] Xu G, Shi H, Ren L, Gou H, Gong D, Gao X, et al. "Enhancing the anti-colon cancer activity of quercetin by self-assembled micelles". International Journal of Nanomedicine. 2015; 10: 2051. https://doi.org/10.2147/IJN.S75550.

[13] Wang W, Sun C, Mao L, Ma P, Liu F, Yang J, Gao Y. "The biological activities, chemical stability, metabolism and delivery systems of quercetin: A review". Trends in Food Science & Technology. 2016; 56: 21-38. https://doi.org/10.1016/j.tifs.2016.07.004.

[14] Damiano S, Sasso A, De Felice B, Di Gregorio I, La Rosa G, Lupoli GA, et al. "Quercetin increases MUC2 and MUC5AC gene expression and secretion in intestinal goblet cell-like LS174T via PLC/PKCα/ERK1-2 pathway". Frontiers in Physiology. 2018; 9: 357. https://doi.org/10.3389/fphys.2018.00357.

[15] Newton RU, Galvao DA. "Exercise in prevention and management of cancer". Current Treatment Options in Oncology. 2008; 9(2): 135-46. https://doi.org/10.1007/s11864-008-0065-1.

[16] Darband SG, Sadighparvar S, Pakdel FG, Naderi S, Majidinia M. "Involvement of IGF/IGFBP/Erk axis in the exercise-mediated preventive effects on colorectal cancer in rats". International Journal of Clinical and Experimental Pathology. 2021; 14(5): 608.

[17] Kim JE, Lee MR, Park JJ, Choi JY, Song BR, Son HJ, et al. "Quercetin promotes gastrointestinal motility and mucin secretion in loperamide-induced constipation of SD rats through regulation of the mAChRs downstream signal". Pharmaceutical Biology. 2018; 56(1): 309-17. https://doi.org/10.1080/13880209.2018.1474932.

[18] Shree A, Islam J, Sultana S. "Quercetin ameliorates reactive oxygen species generation, inflammation, mucus depletion, goblet disintegration, and tumor multiplicity in colon cancer: Probable role of adenomatous polyposis coli, β‐catenin". Phytotherapy Research. 2021; 35(4): 2171-84. https://doi.org/10.1002/ptr.6969.

[19] Volstatova T, Marchica A, Hroncova Z, Bernardi R, Doskocil I, Havlik J. "Effects of chlorogenic acid, epicatechin gallate, and quercetin on mucin expression and secretion in the Caco‐2/HT29‐MTX cell model". Food Science & Nutrition. 2019; 7(2): 492-8. https://doi.org/10.1002/fsn3.818.

[20] Barcelo A, Claustre J, Moro F, Chayvialle J, Cuber J, Plaisancié P. "Mucin secretion is modulated by luminal factors in the isolated vascularly perfused rat colon". Gut. 2018; 46(2): 218-24. https://doi.org/10.1136/gut.46.2.218.