Cyclooxygenase‐2 in cancer: A review

Abstract

Cyclooxygenase-2 (COX-2) is frequently expressed in many types of cancers exerting a pleiotropic and multifaceted role in genesis or promotion of carcinogenesis and cancer cell resistance to chemo-and radiotherapy. COX-2 is released by cancerassociated fibroblasts (CAFs), macrophage type 2 (M2) cells, and cancer cells to the tumor microenvironment (TME). COX-2 induces cancer stem cell (CSC)-like activity, and promotes apoptotic resistance, proliferation, angiogenesis, inflammation, invasion, and metastasis of cancer cells. COX-2 mediated hypoxia within the TME along with its positive interactions with YAP1 and antiapoptotic mediators are all in favor of cancer cell resistance to chemotherapeutic drugs. COX-2 exerts most of the functions through its metabolite prostaglandin E2. In some and limited situations, COX-2 may act as an antitumor enzyme. Multiple signals are contributed to the functions of COX-2 on cancer cells or its regulation. Members of mitogen-activated protein kinase (MAPK) family, epidermal growth factor receptor (EGFR), and nuclear factor-κβ are main upstream modulators for COX-2 in cancer cells. COX-2 also has interactions with a number of hormones within the body. Inhibition of COX-2 provides a high possibility to exert therapeutic outcomes in cancer. Administration of COX-2 inhibitors in a preoperative setting could reduce the risk of metastasis in cancer patients. COX-2 inhibition also sensitizes cancer cells to treatments like radioand chemotherapy. Chemotherapeutic agents adversely induce COX-2 activity. Therefore, choosing an appropriate chemotherapy drugs along with adjustment of the type and does for COX-2 inhibitors based on the type of cancer would be an effective adjuvant strategy for targeting cancer.

Efficacy of a phenol derivative, isopropyl vanillate, as an anti‐inflammatory agent: A new small molecule inhibitor of COX and neutrophil migration

“…This inflammatory response is also mediated by the regulation of proinflammatory cytokines, such as IL‐1β, TNFα, and by the activation of transcription factors, such as NF‐κB). ISP‐VT significantly reduced COX‐2 expression in the subplantar tissue of mice in the count of positively labeled cells for this enzyme when compared to the group treated with carrageenan (Hashemi Goradel, Najafi, Salehi, Farhood, & Mortezaee, ; Wallace & Vong, ; Yu, Lao, & Zheng, ). Our results showed that one of the mechanisms of the anti‐inflammatory activity of ISP‐VT is COX‐2 inhibition.…”

Suppression of MicroRNA-144 Promotes CXCR4 and CXCL12 Expression and Downregulates Apoptosis in Ovarian Cancer Cells

“…Cyclooxygenases (COXs) are cytoplasmic enzymes that catalyze the rate-limiting step of prostaglandin biosynthesis in mediator participating in several biological processes. COX-2 is known to inhibit apoptosis and induce proliferation patterns such as, angiogenesis, inflammation, invasion, and metastasis of cancer cells (Stasinopoulos et al, 2013), (Hashemi Goradel et al, 2019). The present study assessed the suppression of miR-144 is able to markedly activate proliferation and modulate COX-2 expression in ovarian cancer cells.…”

Immunohistochemical detectability of cyclooxygenase‐2 expression in cells of human melanocytic skin lesions: A methodological review

“…High COX‐2 expression is thought to play an important role in tumorigenesis through various mechanisms modulated by increased production of prostaglandins: stimulation of cell proliferation, inhibition of apoptosis, maintenance of cancer stem cell features, increasing of cell invasiveness, enhancement of angiogenesis and affect on immune system. In turn, the COX‐2 peroxidase activity may contribute to production of mutagens (Figure ) …”

“…In turn, the COX-2 peroxidase activity may contribute to production of mutagens ( Figure 1). [5][6][7][8] Enhanced COX-2 expression was demonstrated in various types of human malignancies: carcinomas of colon, 9,10 breast, 11,12 lung, 13,14 stomach, 15,16 esophagus, 17,18 pancreas, 19 bladder, 20 prostate, 21 ovary, 22,23 cervix, 24,25 osteosarcomas, 26,27 gliomas, 28,29 and Hodgkin lymphomas. 30 In most of the studies, it was shown that cancer progression is accompanied by an increase in COX-2 levels and may have prognostic potential.…”