The Role of Cyclooxygenase-2 in Signaling Pathways Promoting Colorectal Cancer

authors:

avatar Abasalt Hosseinzadeh Colagar , * , avatar Abdolvahab Moshtaghian , avatar Tahereh Zahedi


how to cite: Hosseinzadeh Colagar A, Moshtaghian A, Zahedi T. The Role of Cyclooxygenase-2 in Signaling Pathways Promoting Colorectal Cancer. koomesh. 2023;25(1):e152797. 

Abstract

Colorectal cancer is one of the most common cancers in the world. Various factors are involved in the development and progression of this disease. One of these agents is cyclooxygenase-2 (COX-2). COX-2 is a product of the PTGS2 gene and converts free arachidonic acid to prostaglandins. COX-2 is not naturally expressed in most normal cells. Noticeably, the increased expression of COX-2 has been observed in chronic inflammatory diseases and various cancers. COX-2 promotes colorectal cancer through various signaling pathways. COX-2 plays its role in colorectal cancer by induction of Bcl-2 expression, and β-catenin pathway activation, and leads to translocate of the NF-κB from the cytoplasm to the nucleus. NF-κB transcription factor plays an important role in physiological processes such as cell proliferation, cell death, and inflammation. Deregulation of NF-κB and its impact on the signaling pathway play a critical role in the development and progression of colorectal cancer. Another factor that plays a role in the development and progression of colorectal cancer is the β-catenin gene. Mutations in the β-catenin gene have been found in more than half of colorectal cancer patients. Bcl-2 is also known as an anti-apoptotic factor in all types of cancers. COX-2 controls all these pathways. Therefore, targeting COX-2 can be proposed as a therapeutic strategy for the treatment of colorectal cancer. The purpose of this review is to investigate the signaling pathways related to COX-2 in colorectal cancer

References

  • 1.

    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. Cancer J Clin 2010; 60: 277-300.

  • 2.

    Soheilifar MH, Izadi F, Amini R, Saidijam M. Co-regulatory Network of Transcription Factors and miRNAs in Colorectal Cancer Pathogenesis. Iran J Med Sci 2020; 45: 395.

  • 3.

    Soheilifar MH, Moshtaghian A, Maadi H, Izadi F, Saidijam M. BMI1 roles in cancer stem cells and its association with microRNAs dysregulation in cancer: Emphasis on colorectal cancer. Int J Cancer Manag 2018; 11.##https://doi.org/10.5812/ijcm.82926.

  • 4.

    Dolatkhah R, Somi MH, Bonyadi MJ, Asvadi Kermani I, Farassati F, Dastgiri S. Colorectal cancer in Iran: molecular epidemiology and screening strategies. J Cancer Epidemiol 2015; 2015.

  • 5.

    Gupta RA, DuBois RN. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 2001; 1: 11-21.

  • 6.

    Rouzer CA, Marnett LJ. Endocannabinoid oxygenation by cyclooxygenases, lipoxygenases, and cytochromes P450: cross-talk between the eicosanoid and endocannabinoid signaling pathways. Chem Rev 2011; 111: 5899-5921.

  • 7.

    Su CW, Zhang Y, Zhu YT. Stromal COX-2 signaling are correlated with colorectal cancer: A review. Crit Rev Oncol Hematol 2016; 107: 33-38.

  • 8.

    Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 2004; 56: 387-437.

  • 9.

    Obermoser V, Baecker D, Schuster C, Braun V, Kircher B, Gust R. Chlorinated cobalt alkyne complexes derived from acetylsalicylic acid as new specific antitumor agents. Dalton Trans 2018; 47: 4341-4351.

  • 10.

    Nuez F, Bravo S, Cruzat F, Montecino M, De Ferrari GV. Wnt/-catenin signaling enhances cyclooxygenase-2 (COX2) transcriptional activity in gastric cancer cells. PloS One 2011; 6: e18562.

  • 11.

    Kim SH, Ahn BK, Paik SS, Lee KH. Cyclooxygenase-2 expression is a predictive marker for late recurrence in colorectal cancer. Gastroenterol Res Pract 2018; 2018.

  • 12.

    Zahedi T, Colagar AH, Mahmoodzadeh H. PTGS2 over-expression: a colorectal carcinoma initiator not an invasive factor. Rep Biochem Mol Biol 2021; 9: 442.

  • 13.

    Rojas A, Gueorguieva P, Lelutiu N, Quan Y, Shaw R, Dingledine R. The prostaglandin EP1 receptor potentiates kainate receptor activation via a protein kinase C pathway and exacerbates status epilepticus. Neurobiol Dis 2014; 70: 74-89.

  • 14.

    Pozzi A, Yan X, Macias-Perez I, Wei S, Hata AN, Breyer RM, et al. Colon carcinoma cell growth is associated with prostaglandin E2/EP4 receptor-evoked ERK activation. J Biol Chem 2004; 279: 29797-29804.

  • 15.

    Wang D, Mann JR, Dubois RN. The role of prostaglandins and other eicosanoids in the gastrointestinal tract. Gastroenterology 2005; 128: 1445-1461.

  • 16.

    Zhu Y, Zhu M, Lance P. IL1-mediated stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithelial cancer cells. Exp Cell Res 2012; 318: 2520-2530.

  • 17.

    Zhu Y, Hua P, Lance P. Cyclooxygenase-2 expression and prostanoid biogenesis reflect clinical phenotype in human colorectal fibroblast strains. Cancer Res 2003; 63: 522-526.

  • 18.

    Park JY, Pillinger MH, Abramson SB. Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clin Immunol 2006; 119: 229-240.

  • 19.

    Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, et al. Suppression of intestinal polyposis in Apc716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996; 87: 803-809.

  • 20.

    Gurram B, Zhang S, Li M, Li H, Xie Y, Cui H, et al. Celecoxib conjugated fluorescent probe for identification and discrimination of cyclooxygenase-2 enzyme in cancer cells. Anal Chem 2018; 90: 5187-5193.

  • 21.

    Raj V, Bhadauria AS, Singh AK, Kumar U, Rai A, Keshari AK, et al. Novel 1, 3, 4-thiadiazoles inhibit colorectal cancer via blockade of IL-6/COX-2 mediated JAK2/STAT3 signals as evidenced through data-based mathematical modeling. Cytokine 2019; 118: 144-159.

  • 22.

    Mortezaee K. Human hepatocellular carcinoma: Protection by melatonin. J Cell Physiol 2018; 233: 6486-6508.

  • 23.

    Dannenberg AJ, Lippman SM, Mann JR, Subbaramaiah K, DuBois RN. Cyclooxygenase-2 and epidermal growth factor receptor: pharmacologic targets for chemoprevention. J Clin Oncol 2005; 23: 254-266.

  • 24.

    Mutoh M, Watanabe K, Kitamura T, Shoji Y, Takahashi M, Kawamori T, et al. Involvement of prostaglandin E receptor subtype EP4 in colon carcinogenesis. Cancer Res 2002; 62: 28-32.

  • 25.

    Ashraf A, Ashoorian Y, Habibi M, Nejatifar F, Esmaeili Delshad MS, Samimian S, et al. Correlation between the degree and stage of malignancy with environmental factors based on gender and age of patients in colorectal cancer patients. Koomesh 2022; 24: 118-127. (Persian).

  • 26.

    Miladinov-Mikov M. Colorectal cancer epidemiology. Eur J Cancer 2010; 46: 765-781.

  • 27.

    Thanikachalam K, Khan G. Colorectal Cancer and Nutrition. Nutrients 2019; 11.

  • 28.

    Hu D, Zhang M, Wang S, Wang Z. High expression of cyclooxygenase 2 is an indicator of prognosis for patients with esophageal squamous cell carcinoma after I vor L ewis esophagectomy. Thoracic Cancer 2016; 7: 310-315.

  • 29.

    Uefuji K, Ichikura T, Mochizuki H. Cyclooxygenase-2 expression is related to prostaglandin biosynthesis and angiogenesis in human gastric cancer. Clin Cancer Res 2000; 6: 135-138.

  • 30.

    Sheng J, Sun H, Yu FB, Li B, Zhang Y, Zhu YT. The role of cyclooxygenase-2 in colorectal cancer. Int J Med Sci 2020; 17: 1095.

  • 31.

    Zhao Q, Wang C, Zhu J, Wang L, Dong S, Zhang G, Tian J. RNAi-mediated knockdown of cyclooxygenase2 inhibits the growth, invasion and migration of SaOS2 human osteosarcoma cells: a case control study. J Exp Clin Cancer Res 2011; 30: 1-9.

  • 32.

    Qu L, Liu B. Cyclooxygeanse-2 promotes metastasis in osteosarcoma. Cancer Cell Int 2015; 15: 1-4.

  • 33.

    Regulski M, Regulska K, Prukaa W, Piotrowska H, Stanisz B, Murias M. COX-2 inhibitors: a novel strategy in the management of breast cancer. Drug Discov Today 2016; 21: 598-615.

  • 34.

    Liu B, Shi ZL, Feng J, Tao HM. Celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma cell line MG-63 via down-regulation of PI3K/Akt. Cell Biol Int 2008; 32: 494-501.

  • 35.

    Wang D, DuBois RN. Eicosanoids and cancer. Nat Rev Cancer 2010; 10: 181-193.

  • 36.

    Poligone B, Baldwin AS. Positive and negative regulation of NF-B by COX-2: roles of different prostaglandins. J Biol Chem 2001; 276: 38658-38664.

  • 37.

    Khatami SS, Tavakoli F, Bagheri H, Salarinia R, Hesari A, Ghasemi F. Effects of fibromodulin protein expression on NFkB and TGF signaling pathways in liver cancer cells. Koomesh 2020; 22: 529-533. (Persian).##https://doi.org/10.29252/koomesh.22.3.529.

  • 38.

    Spehlmann ME, Eckmann L. Nuclear factor-kappa B in intestinal protection and destruction. Curr Opin Gastroenterol 2009; 25: 92-9.

  • 39.

    Al-Ashy R, Chakroun I, El-Sabban M, Homaidan FR. The role of NF-B in mediating the anti-inflammatory effects of IL-10 in intestinal epithelial cells. Cytokine 2006; 36: 1-8.

  • 40.

    Ghosh S, May MJ, Kopp EB. NF-(kappa) B and REL proteins: Evolutionarily conserved mediators of immune responses. Ann Rev Immunol 1998; 16: 225.

  • 41.

    Soleimani A, Rahmani F, Ferns GA, Ryzhikov M, Avan A, Hassanian SM. Role of the NF-B signaling pathway in the pathogenesis of colorectal cancer. Gene 2020; 726: 144132.

  • 42.

    Sun P, Quan JC, Wang S, Zhuang M, Liu Z, Guan X, et al. lncRNA-PACER upregulates COX-2 and PGE2 through the NF-B pathway to promote the proliferation and invasion of colorectal-cancer cells. Gastroenterol Rep 2021; 9: 257-268.

  • 43.

    Rossi A, Kapahi P, Natoli G, Takahashi T, Chen Y, Karin M, Santoro MG. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IB kinase. Nature 2000; 403: 103-108.

  • 44.

    Sheng H, Shao J, Washington MK, DuBois RN. Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem 2001; 276: 18075-18081.

  • 45.

    Madrid LV, Wang CY, Guttridge DC, Schottelius AJ, Baldwin Jr AS, Mayo MW. Akt suppresses apoptosis by stimulating the transactivation potential of the RelA/p65 subunit of NF-B. Mol Cell Biol 2000; 20: 1626-1638.

  • 46.

    Ye Y, Wu W, Shin V, Bruce I, Wong B, Cho C. Dual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smoke. Carcinogenesis 2005; 26: 827-834.

  • 47.

    Gomez PF, Pillinger MH, Attur M, Marjanovic N, Dave M, Park J, et al. Resolution of inflammation: prostaglandin E2 dissociates nuclear trafficking of individual NF-B subunits (p65, p50) in stimulated rheumatoid synovial fibroblasts. J Immunol 2005; 175: 6924-6930.

  • 48.

    Ozawa M, Baribault H, Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J 1989; 8: 1711-1717.

  • 49.

    Stamos JL, Weis WI. The -catenin destruction complex. Cold Spring Harbor Perspect Biol 2013; 5: a007898.

  • 50.

    Wang B, Li X, Liu L, Wang M. -Catenin: oncogenic role and therapeutic target in cervical cancer. Biol Res 2020; 53: 1-11.

  • 51.

    Cheng X, Xu X, Chen D, Zhao F, Wang W. Therapeutic potential of targeting the Wnt/-catenin signaling pathway in colorectal cancer. Biomed Pharm 2019; 110: 473-481.

  • 52.

    Ramesh P, Medema JP. BCL-2 family deregulation in colorectal cancer: potential for BH3 mimetics in therapy. Apoptosis 2020; 25: 305-320.

  • 53.

    Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin--catenin signaling axis. Science 2005; 310: 1504-1510.

  • 54.

    Campbell KJ, Tait SW. Targeting BCL-2 regulated apoptosis in cancer. Open Biol 2018; 8: 180002.