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:: Volume 32, Issue 1 (Spring 2022) ::
MEDICAL SCIENCES 2022, 32(1): 31-43 Back to browse issues page
Effects of GW9508 small molecule on oxidative stress enzymes in colorectal cancer and non-cancerous HUVEC cells
Behnoosh Rafienia1 , Elham Hoveizi 2, Ali Shahriari3
1- Student, Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
2- Associate Professor, Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran , e.hoveizi@yahoo.com
3- Associate Professor, Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Iran
Abstract:   (681 Views)
Background: In this study, we aimed to evaluate the effects of GW9508 as an unsaturated fatty acid on inducing oxidative stress in HT-29 cancer cell line and non-cancer HUVEC cells.
Materials and methods: The effects of GW9508 on cell viability were determined by performing MTT assay after 1, 3 and 5 days. The anti-oxidant superoxide dismutase (SOD) and catalase enzymes' assay was performed to evaluate the apoptosis. Moreover, inverted microscope and DAPI staining were applied to measure the changes in cell and nucleus morphology.
Results: The IC50 dose of GW9508 was 500 µM in both cancer and normal cells. Results of enzymatic activity assay exhibited the increscent of activity of catalase and SOD in treated cells led to promoting apoptosis in cells. The amount of activities of SOD and catalase in HT-29 treated cells that were calculated 1.254 and 0.338 mU/mg respectively, which had a significant increase compared to activities of these two enzymes in control cells (0.85 and 0.206 mU/mg, respectively) (p≤0.05). There was also a significant increase in the activities of SOD and catalase in HUVEC treated cells (1.111 and 0.517 mU/mg) compared to the activities of the two enzymes in the control group, which were calculated 0.755 and 0.184 mU/mg, respectively.
Conclusion: GW9508 small molecule induces oxidative stress and ROS production in HT-29 and HUVEC cells, leading to cytotoxicity and thus promoting apoptotic cell death in cancer cells. However, these effects are contingent upon dose and the type of cell lineages.
 
Keywords: Colorectal cancer, Unsaturated fatty acid, Small molecule, Oxidative stress
Full-Text [PDF 612 kb]   (190 Downloads)    
Semi-pilot: Experimental | Subject: Animal Biology
Received: 2020/05/14 | Accepted: 2021/12/29 | Published: 2022/03/21
References
1. Hoseini S, Moaddabshoar L, Hemati S, Mohammadianpanah M. An Overview of Clinical and Pathological Characteristics and Survival Rate of Colorectal Cancer in Iran. Ann Color Res 2014; 2:1-8. 2. Ghobrial IM, Witzig TE, Adjei AA. Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin 2005; 55:178-94. https://doi.org/10.3322/canjclin.55.3.178 3. Chun J, Kang M, Kim YS. A triterpenoid saponin from Adenophora triphylla var. japonica suppresses the growth of human gastric cancer cells via regulation of apoptosis and autophagy. Tumour Biol 2014;35:12021-30. https://doi.org/10.1007/s13277-014-2501-0 [DOI:10.17795/acr-17264]
2. Fauser JK, Prisciandaro LD, Cummins AG, Howarth GS. Fatty acids as potential adjunctive colorectal chemotherapeutic agents. Cancer Biol Ther 2011; 11:724-31. [DOI:10.4161/cbt.11.8.15281]
3. Fulda S, Galluzzi L, Kroemer G. Targeting mitochondria for cancer therapy. Nat Rev Drug Discov 2010; 9:447. [DOI:10.1038/nrd3137]
4. esik SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer 2005;5:876-85 [DOI:10.1038/nrc1736]
5. Fujita T, Matsuoka T, Honda T, Kabashima K, Hirata T, Narumiya S. A GPR40 agonist GW9508 suppresses CCL5, CCL17, and CXCL10 induction in keratinocytes and attenuates cutaneous immune inflammation. J Invest Dermatol 2011; 131:1660-7. [DOI:10.1038/jid.2011.123]
6. Fukushima K, Yamasaki E, Ishii S, Tomimatsu A, Takahashi K. Biochemical and Biophysical Research Communications Different roles of GPR120 and GPR40 in the acquisition of malignant properties in pancreatic cancer cells. Biochem Biophys Res Commun 2015; 8-11. [DOI:10.1016/j.bbrc.2015.08.050]
7. Gao B, Huang Q, Jie Q, Wang L, Zhang H, Liu J, et al. Biochimie Dose-response estrogen promotes osteogenic differentiation via GPR40 (FFAR1) in murine BMMSCs. Biochimie 2015;110:36-44. [DOI:10.1016/j.biochi.2015.01.001]
8. Philippe C, Wauquier F, Léotoing L, Coxam V, Wittrant Y. GW9508 , a free fatty acid receptor agonist , speci fi cally induces cell death in bone resorbing precursor cells through increased oxidative stress from mitochondrial origin. Exp Cell Res 2013; 319:3035-41. [DOI:10.1016/j.yexcr.2013.08.013]
9. Pierre AS, Minville-Walz M, Fèvre C, Hichami A, Gresti J, Pichon L, et al. Trans-10, cis-12 conjugated linoleic acid induced cell death in human colon cancer cells through reactive oxygen species-mediated ER stress. Biochim Biophys Acta 2013;1831:759-68. [DOI:10.1016/j.bbalip.2013.01.005]
10. Fauser JK, Matthews GM, Cummins AG, Howarth GS. Induction of Apoptosis by the Medium-Chain Length Fatty Acid Lauric Acid in Colon Cancer Cells due to Induction of Oxidative Stress. Chemotherapy 2013; 59: 214-24. [DOI:10.1159/000356067]
11. Wang J, Yi J. Cancer cell killing via ROS: To increase or decrease; that is a question. Cancer Biol Ther 2008; 7:1875-84. [DOI:10.4161/cbt.7.12.7067]
12. Dodson M, Darley-Usmar V, Zhang J. Cellular metabolic and autophagic pathways: traffic control by redox signaling. Free Radic Biol Med 2013; 63:207-21. [DOI:10.1016/j.freeradbiomed.2013.05.014]
13. Wen X, Wu J, Wang F, Liu B, Huang C, Wei Y. Free Radical Biology and Medicine Deconvoluting the role of reactive oxygen species and autophagy in human diseases. Free Radic Biol Med 2013; 65:402-10. [DOI:10.1016/j.freeradbiomed.2013.07.013]
14. Kono Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 1978; 186:189-95. [DOI:10.1016/0003-9861(78)90479-4]
15. Koroliuk MA, Ivanova LI, Maĭorova IG, Tokarev VE. Metod opredeleniia aktivnosti katalazy [A method of determining catalase activity]. Lab Delo 1988:16-9. [In Russian]
16. Alcindor T, Beauger N. Oxaliplatin: a review in the era of molecularly targeted therapy. Curr Oncol 2011;18:18. [DOI:10.3747/co.v18i1.708]
17. Stordal B, Pavlakis N, Davey R. Oxaliplatin for the treatment of cisplatin-resistant cancer: a systematic review. Cancer Treat Rev 2007; 33:347-57. [DOI:10.1016/j.ctrv.2007.01.009]
18. Conklin KA. Dietary polyunsaturated fatty acids: impact on cancer chemotherapy and radiation. Altern Med Rev 2002; 7:4-22.
19. Serini S, Piccioni E, Merendino N, Calviello G. Dietary polyunsaturated fatty acids as inducers of apoptosis: implications for cancer. Apoptosis 2009; 14:135-52. [DOI:10.1007/s10495-008-0298-2]
20. Palombo JD, Ganguly A, Bistrian BR, Menard MP. The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells. Cancer Lett 2002; 177:163-72. [DOI:10.1016/S0304-3835(01)00796-0]
21. Cho HJ, Kim EJ, Lim SS, Kim MK, Sung M-K, Kim J-S, et al. Trans-10, cis-12, not cis-9, trans-11, conjugated linoleic acid inhibits G1-S progression in HT-29 human colon cancer cells. J Nutr 2006; 136:893-8. [DOI:10.1093/jn/136.4.893]
22. Cesano A, Visonneau S, Scimeca JA, Kritchevsky D, Santoli D. Opposite effects of linoleic acid and conjugated linoleic acid on human prostatic cancer in SCID mice. Anticancer Res 1998; 18:1429-34.
23. Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. JNCI J Natl Cancer Inst 1981; 66:1192-308. [DOI:10.1093/jnci/66.6.1192]
24. Milligan G, Shimpukade B, Ulven T, Hudson BD. Complex pharmacology of free fatty acid receptors. Chem Rev 2016; 117:67-110. [DOI:10.1021/acs.chemrev.6b00056]
25. Fan Y-Y, Ran Q, Toyokuni S, Okazaki Y, Callaway ES, Lupton JR, et al. Dietary fish oil promotes colonic apoptosis and mitochondrial proton leak in oxidatively stressed mice. Cancer Prev Res 2011; 4:1267-74. [DOI:10.1158/1940-6207.CAPR-10-0368]
26. Wu Q, Wang H, Zhao X, Shi Y, Jin M, Wan B, et al. Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma. Oncogene 2013; 32: 5541-5550. [DOI:10.1038/onc.2013.264]
27. Touil Y, Igoudjil W, Corvaisier M, Dessein A-F, Vandomme J, Monté D, et al. Colon cancer cells escape 5FU chemotherapy-induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis. Clin cancer Res 2014; 20:837-46. [DOI:10.1158/1078-0432.CCR-13-1854]
28. Park HS, Ryu JH, Ha YL, Park JHY. Dietary conjugated linoleic acid (CLA) induces apoptosis of colonic mucosa in 1, 2-dimethylhydrazine-treated rats : A possible mechanism of the anticarcinogenic effect by CLA. Br J Nutr 2011; 86:549-55. [DOI:10.1079/BJN2001445]
29. Kuniyasu H, Yoshida K, Sasaki T, Sasahira T, Fujii K, Ohmori H. Conjugated linoleic acid inhibits peritoneal metastasis in human gastrointestinal cancer cells Int J Cancer 2006; 576:571-6. [DOI:10.1002/ijc.21368]
30. Rajakangas J, Basu S, Salminen I, Mutanen M. Adenoma growth stimulation by the trans-10, cis-12 isomer of conjugated linoleic acid (CLA) is associated with changes in mucosal NF-κB and cyclin D1 protein levels in the Min mouse. J Nutr 2003; 133:1943-8. [DOI:10.1093/jn/133.6.1943]
31. Fliss MS, Usadel H, Caballero OL, Wu L, Buta MR, Eleff SM, et al. Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science 2000; 287:2017-9. [DOI:10.1126/science.287.5460.2017]
32. Kang D, Hamasaki N. Mitochondrial oxidative stress and mitochondrial DNA. Clin Chem Lab Med 2003; 41:1281-8. [DOI:10.1515/CCLM.2003.195]
33. Vafa O, Wade M, Kern S, Beeche M, Pandita TK, Hampton GM, et al. c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability. Mol Cell 2002; 9:1031-44. [DOI:10.1016/S1097-2765(02)00520-8]
34. Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resist Updat 2004; 7:97-110. doi: 10.1016/j.drup.2004.01.004. [DOI:10.1016/j.drup.2004.01.004]
35. Fojo T. p53 as a therapeutic target: unresolved issues on the road to cancer therapy targeting mutant p53. Drug Resist Updat 2002; 5:209-16. [DOI:10.1016/S1368-7646(02)00119-X]
36. Sastre J, Pallardó F V, Viña J. Mitochondrial oxidative stress plays a key role in aging and apoptosis. IUBMB Life 2000; 49:427-35. [DOI:10.1080/152165400410281]
37. Hsu Y, Ip MM. Conjugated linoleic acid-induced apoptosis in mouse mammary tumor cells is mediated by both G protein coupled receptor-dependent activation of the AMP-activated protein kinase pathway and by oxidative stress. Cell Signal 2020; 23:2013-20. [DOI:10.1016/j.cellsig.2011.07.015]
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Rafienia B, Hoveizi E, Shahriari A. Effects of GW9508 small molecule on oxidative stress enzymes in colorectal cancer and non-cancerous HUVEC cells. MEDICAL SCIENCES. 2022; 32 (1) :31-43
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Volume 32, Issue 1 (Spring 2022) Back to browse issues page
فصلنامه علوم پزشکی دانشگاه آزاد اسلامی واحد پزشکی تهران Medical Science Journal of Islamic Azad Univesity - Tehran Medical Branch
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