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Impact assessment of Sclareol on endoplasmic reticulum stress in KATO III human gastric carcinoma cancer cell lines
Mojtaba Ghaffarian Gabalou1 , Seyed Ali Rahmani2 , Changiz Ahmadizadeh3 , Rasoul Sharifi4
1- Department of Molecular Genetics, Ah.C., Islamic Azad University, Ahar, Iran
2- Department of Molecular Genetics, Ah.c , Islamic Azad University, Ahar, Iran , rahmaniseyedali@yahoo.com
3- Department of Microbiology, Ah.c , Islamic Azad University, Ahar, Iran
4- Department of biochemistry, Ah.c , Islamic Azad University, Ahar, Iran
Abstract:   (1267 Views)
Introduction and objectives: The main goals of chemotherapy are to increase apoptosis or cell death and to stop the cell cycle in cancer cells. One of the very important factors inducing apoptosis in cancer cells is to increase the stress of the endoplasmic reticulum system. In this study, the authors intended to investigate the effect of Sclareol on the ATF6 pathway as well as the effect of two other sub-genes, VEGF and E2F1, associated with the UPR pathways.
Materials and methods: The target population in this research was KATO III human gastric carcinoma cancer cells, which were purchased from the Pasteur Institute of Iran, and they were cultured in the cell culture laboratory until their number reached at least 100,000 cells/well. The cells were treated with concentrations of 0, 20, 40, 60, 80 and 100 μM of Sclareol for 5 hours. Analyzing the expression of the genes- expressed in the research objectives- derived from gastric cancer cells before and after treatment with Sclareol was performed using Quantitative Real Time-PCR from the spheres of cell lines cultured in suspension.
Results: ATF-6 gene expression significantly increased in genes with doses of 20, 40 and 60 μM of Sclareol (P<0.0001). On the other hand, it was shown that the level of VEGF gene expression was significantly reduced in genes with doses of 20, 40 and 60 μM of Sclareol (P<0.001). Also, there was a significant increase in E2F1 gene expression in doses of 20, 40 and 60 μM of Sclareol (P<0.003).

 
Keywords: Gastric Cancer- The Endoplasmic Reticulum System Stress- Sclareol - KATO III Gastric Cancer Cells
Full-Text [PDF 802 kb]   (336 Downloads)    
Research Article: Research Article | Subject: Human Genetics
Received: 2024/11/13 | Accepted: 2025/06/8
References
1. Conti CB, Agnesi S, Scaravaglio M, Masseria P, Dinelli ME, Oldani M, et al. Early gastric cancer: update on prevention, diagnosis and treatment. Int J Environ Res Public Health. 2023;20(3):2149. [View at Publisher] [DOI] [PMID] [Google Scholar]
2. Gullo I, Grillo F, Mastracci L, Vanoli A, Carneiro F, Saragoni L, et al. Precancerous lesions of the stomach, gastric cancer and hereditary gastric cancer syndromes. Pathologica. 2020;112(3):166-85. [View at Publisher] [DOI] [PMID] [Google Scholar]
3. Ilic M, Ilic I. Epidemiology of stomach cancer. World J Gastroenterol. 2022;28(12):1187-203. [View at Publisher] [DOI] [PMID] [Google Scholar]
4. Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM. Gastric adenocarcinoma: review and considerations for future directions. Ann Surg. 2005;241(1):27-39. [View at Publisher] [DOI] [PMID] [Google Scholar]
5. Ebrahimi Z, Shateri Z, Nouri M, Sikaroudi MK, Masoodi M, Shidfar F, et al. Ultra-processed food intake and risk of Helicobacter pylori infection: a case-control study. Food Sci Nutr. 2024;12(7):5019-26. [View at Publisher] [DOI] [PMID] [Google Scholar]
6. Dolatkhah H, Movahedian A, Somi M-H, Aghaei M, Samadi N, Mirza-Aghazade A, et al. Effect of PUFAs oral administration on the amount of apoptotic caspases enzymes in gastric cancer patients undergoing chemotherapy. Anticancer Agents Med Chem. 2017;17(1):93-101. [View at Publisher] [DOI] [PMID] [Google Scholar]
7. Farhood B, Geraily G, Alizadeh A. Incidence and mortality of various cancers in Iran and compare to other countries: a review article. Iran J Public Health. 2018;47(3):309-16. [View at Publisher] [PMID] [Google Scholar]
8. Tringali A, Giannetti A, Adler DG. Endoscopic management of gastric outlet obstruction disease. Ann Gastroenterol. 2019;32(4):330-7. [View at Publisher] [DOI] [PMID] [Google Scholar]
9. Garg P, Malhotra J, Kulkarni P, Horne D, Salgia R, Singhal SS. Emerging therapeutic strategies to overcome drug resistance in cancer cells. Cancers (Basel). 2024;16(13):2478. [View at Publisher] [DOI] [PMID] [Google Scholar]
10. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Chapter 13: Intracellular vesicular traffic. In: Molecular biology of the cell. 4th ed. New York: Garland Science; 2002. [View at Publisher] [Google Scholar]
11. Adams BM, Canniff NP, Guay KP, Hebert DN. The role of endoplasmic reticulum chaperones in protein folding and quality control. Prog Mol Subcell Biol. 2021;59:27-50. [View at Publisher] [DOI] [PMID] [Google Scholar]
12. Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature. 2008;454(7203):455-62. [View at Publisher] [DOI] [PMID] [Google Scholar]
13. Ni M, Zhang Y, Lee AS. Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting. Biochem J. 2011;434(2):181-8. [View at Publisher] [DOI] [PMID] [Google Scholar]
14. Noori S, Hassan ZM, Mohammadi M, Habibi Z, Sohrabi N, Bayanolahgh S. Sclareol modulates the Treg intra-tumoral infiltrated cell and inhibits tumor growth in vivo. Cell Immunol. 2010;263(2):148-53. [View at Publisher] [DOI] [PMID] [Google Scholar]
15. Afshari H, Nourbakhsh M, Salehi N, Mahboubi-Rabbani M, Zarghi A, Noori S. STAT3-mediated apoptotic-enhancing function of sclareol against breast cancer cells and cell sensitization to cyclophosphamide. Iran J Pharm Res. 2020;19(1):398-412. [View at Publisher] [DOI] [PMID] [Google Scholar]
16. Vandghanooni S, Farajzadeh Vahid Z, Nakhlband A, Bahadori MB, Eskandani M. Sclareol inhibits hypoxia-inducible factor-1α accumulation and induces apoptosis in hypoxic cancer cells. Adv Pharm Bull. 2022;12(3):593-602. [View at Publisher] [DOI] [PMID] [Google Scholar]
17. Talib WH, Alsayed AR, Barakat M, Abu-Taha MI, Mahmod AI, Ismail Mahmod A. Targeting drug chemo-resistance in cancer using natural products. Biomedicines. 2021;9(10):1353. [View at Publisher] [DOI] [PMID] [Google Scholar]
18. Aboutalebi E, Sakhinia E, Beilanokhi V, Dolatkhah H. Investigating the effect of sclareol on IRE-1 and PERK genes in the pathway of endoplasmic reticulum stress in gastric cancer cells MKN-45. J Res Appl Basic Med Sci. 2020;6(1):32-44. [View at Publisher] [Google Scholar]
19. Pisa R, Kapoor TM. Chemical strategies to overcome resistance against targeted anticancer therapeutics. Nat Chem Biol. 2020;16(8):817-25. [View at Publisher] [DOI] [PMID] [Google Scholar]
20. Zhou J, Xie X, Tang H, Peng C, Peng F. The bioactivities of sclareol: a mini review. Front Pharmacol. 2022;13:1014105. [View at Publisher] [DOI] [PMID] [Google Scholar]
21. Hassan ZM, Yaraee R, Zare N, Ghazanfari T, Sarraf Nejad AH, Nazori B. Immunomodulatory effect of R10 fraction of garlic extract on natural killer activity. Int Immunopharmacol. 2003;3(10-11):1483-9. [View at Publisher] [DOI] [PMID] [Google Scholar]
22. Yuan S, She D, Jiang S, Deng N, Peng J, Ma L. Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer. Mol Med. 2024;30(1):40. [View at Publisher] [DOI] [PMID] [Google Scholar]
23. Bonsignore G, Martinotti S, Ranzato E. Endoplasmic reticulum stress and cancer: could unfolded protein response be a druggable target for cancer therapy? Int J Mol Sci. 2023;24(2):1566. [View at Publisher] [DOI] [PMID] [Google Scholar]
24. Kim C, Kim B. Anti-cancer natural products and their bioactive compounds inducing ER stress-mediated apoptosis: a review. Nutrients. 2018;10(8):1021. [View at Publisher] [DOI] [PMID] [Google Scholar]
25. Karayiannakis AJ, Syrigos KN, Polychronidis A, Zbar A, Kouraklis G, Simopoulos C, et al. Circulating VEGF levels in the serum of gastric cancer patients: correlation with pathological variables, patient survival, and tumor surgery. Ann Surg. 2002;236(1):37-42. [View at Publisher] [DOI] [PMID] [Google Scholar]
26. Amirchaghmaghi E, Rezaei A, Moini A, Roghaei MA, Hafezi M, Aflatoonian R. Gene expression analysis of VEGF and its receptors and assessment of its serum level in unexplained recurrent spontaneous abortion. Cell J. 2015;16(4):538-45. [View at Publisher] [DOI] [PMID] [Google Scholar]
27. Morishima N, Nakanishi K, Nakano A. Activating transcription factor-6 (ATF6) mediates apoptosis with reduction of myeloid cell leukemia sequence 1 (Mcl-1) protein via induction of WW domain binding protein 1. J Biol Chem. 2011;286(40):35227-35. [View at Publisher] [DOI] [PMID] [Google Scholar]
28. Lei Y, Yu H, Ding S, Liu H, Liu C, Fu R. Molecular mechanism of ATF6 in unfolded protein response and its role in disease. Heliyon. 2024;10(5):e25937. [View at Publisher] [DOI] [PMID] [Google Scholar]
29. Sano R, Reed JC. ER stress-induced cell death mechanisms. Biochim Biophys Acta. 2013;1833(12):3460-70. [View at Publisher] [DOI] [PMID] [Google Scholar]
30. Fang Z, Lin M, Li C, Liu H, Gong C. A comprehensive review of the roles of E2F1 in colon cancer. Am J Cancer Res. 2020;10(3):757-68. [View at Publisher] [PMID] [Google Scholar]
31. Montecillo-Aguado M, Tirado-Rodriguez B, Huerta-Yepez S. The involvement of polyunsaturated fatty acids in apoptosis mechanisms and their implications in cancer. Int J Mol Sci. 2023;24(14):11691. [View at Publisher] [DOI] [PMID] [Google Scholar]
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