Growth Stimulation and Epidermal Growth Factor Receptor Induction in Cyclooxygenase-Overexpressing Human Colon Carcinoma Cells

Yoshimoto, Tanihiro; Takahashi, Yoshitaka; Kinoshita, Takahiro; Sakashita, Toshiki; Inoue, H.; Tanabe, Tadashi

doi:10.1007/978-1-4615-0193-0_62

Cited by 27 publications

(10 citation statements)

References 13 publications

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“…In addition, many reports of colorectal tumor cells either overexpressing COX-2 or having it silenced have correlated increased COX-2 expression with their invasive and metastatic properties in xenografted tumors in mice (Tsujii and Dubois, 1995;Tsujii et al, 1997;O'mahony et al, 1999;Chen et al, 2001;Sun et al, 2002;Yoshimoto et al, 2002;Charames and Bapat, 2006;Strillacci et al, 2006;Stamatakis et al, 2015). However, the molecular mechanisms by which COX-2 expression in intestinal epithelial cells leads to that phenotype have not been fully elucidated yet.…”

Section: Cox-2 In Colorectal Cancermentioning

confidence: 99%

Cyclooxygenase 2-Regulated Genes an Alternative Avenue to the Development of New Therapeutic Drugs for Colorectal Cancer

et al. 2020

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Colorectal cancer (CRC) is one of the most common and recurrent types of cancer, with high mortality rates. Several clinical trials and meta-analyses have determined that the use of pharmacological inhibitors of cyclooxygenase 2 (COX-2), the enzyme that catalyses the rate-limiting step in the synthesis of prostaglandins (PG) from arachidonic acid, can reduce the incidence of CRC as well as the risk of recurrence of this disease, when used together with commonly used chemotherapeutic agents. These observations suggest that inhibition of COX-2 may be useful in the treatment of CRC, although the current drugs targeting COX-2 are not widely used since they increase the risk of health complications. To overcome this difficulty, a possibility is to identify genes regulated by COX-2 activity that could give an advantage to the cells to form tumors and/or metastasize. The modulation of those genes as effectors of COX-2 may cancel the beneficial effects of COX-2 in tumor transformation and metastasis. A review of the available databases and literature and our own data have identified some interesting molecules induced by prostaglandins or COX-2 that have been also described to play a role in colon cancer, being thus potential pharmacological targets in colon cancer. Among those mPGES-1, DUSP4, and 10, Programmed cell death 4, Trop2, and many from the TGFb and p53 pathways have been identified as genes upregulated in response to COX-2 overexpression or PGs in colon carcinoma lines and overexpressed in colon tumor tissue. Here, we review the available evidence of the potential roles of those molecules in colon cancer in the context of PG/ COX signaling pathways that could be critical mediators of some of the tumor growth and metastasis advantage induced by COX-2. At the end, this may allow defining new therapeutic targets/drugs against CRC that could act specifically against tumor cells and would be effective in the prevention and treatment of CRC, lacking the unwanted side effects of COX-2 pharmacological inhibitors, providing alternative approaches in colon cancer.

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Section: Cox-2 In Colorectal Cancermentioning

confidence: 99%

Cyclooxygenase 2-Regulated Genes an Alternative Avenue to the Development of New Therapeutic Drugs for Colorectal Cancer

et al. 2020

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“…Both COX-2 and epidermal growth factor receptor (EGFR) pathways are activated in most human cancers. 60 The observation that forced expression of COX-2 in human colorectal cancer (CRC) cells stimulates cellular proliferation through induction of EGFR 61 indicated the likelihood of Figure 1 Overview of prostaglandin (PG) synthesis and main functions. Arachidonic acid can be metabolised through three major pathways.…”

Section: Egfr Pathwaymentioning

confidence: 99%

Prostaglandins and Cancer

Wang

DuBois²

2006

Gut

777

660

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SUMMARYChemoprevention has been considered as a possible approach for cancer prevention. A significant effort has been made in the development of novel drugs for both cancer prevention and treatment over the past decade. Recent epidemiological studies and clinical trials indicate that long term use of aspirin and similar agents, also called non-steroidal anti-inflammatory drugs (NSAIDs), can decrease the incidence of certain malignancies, including colorectal, oesophageal, breast, lung, and bladder cancers. The best known targets of NSAIDs are cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandins (PGs) and thromboxane. COX-2 derived prostaglandin E 2 (PGE 2 ) can promote tumour growth by binding its receptors and activating signalling pathways which control cell proliferation, migration, apoptosis, and/or angiogenesis. However, the prolonged use of high dosages of COX-2 selective inhibitors (COXIBs) is associated with unacceptable cardiovascular side effects. Thus it is crucial to develop more effective chemopreventive agents with minimal toxicity. Recent efforts to identify the molecular mechanisms by which PGE 2 promotes tumour growth and metastasis may provide opportunities for the development of safer strategies for cancer prevention and treatment.

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“…2). Thus in colorectal carcinoma cells, COX‐2 overexpression has been shown to stimulate cellular proliferation through induced expression of the EGF receptor 60 . Also in colorectal carcinoma cells, combined treatment with the COX‐2 inhibitor celecoxib and a monoclonal antibody blocking the Her‐2/neu pathway resulted in additive growth inhibition 61 .…”

Section: Cox‐2 and Tumour Cell Proliferationmentioning

confidence: 99%

The role of apoptosis in therapy and prophylaxis of epithelial tumours by nonsteroidal anti-inflammatory drugs (NSAIDs)

et al. 2007

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In addition to having anti-inflammatory activities, nonsteroidal anti-inflammatory drugs (NSAIDs) also inhibit neoplastic cell proliferation by inducing apoptosis. Diclofenac is the anti-neoplastic compound in diclofenac 3% gel (Solaraze) used for topical treatment of actinic keratosis (AK). Main target of NSAIDs seems to be the inhibition of cyclo-oxygenase-2 (COX-2), which is overexpressed in several epithelial tumours and catalyses the synthesis of prostaglandins. The precise mechanism of action of diclofenac in cutaneous cells is still unclear, but induction of apoptosis is a key effect of anti-neoplastic drugs, including NSAIDs. In this paper we give an overview of the anti-tumoural activities of NSAIDs with emphasis on induction of apoptosis. Cyclo-oxygenase-2-mediated synthesis of prostaglandin E(2) (PGE(2)) leads to activation of mitogen-activated protein kinase (MAPK), as well as phosphatidylinositol 3-kinase (PI3K)/Akt pathways. Induction of the anti-apoptotic Bcl-2 and Mcl-1, as well as activation of the caspase-8 inhibitor cFLIP have been reported. In addition, altered lipid concentrations in the cytoplasmic membrane may modulate death receptor activities. Downregulation of both the intrinsic mitochondrial and the extrinsic pathways have been reported. Our data demonstrate induced apoptosis and activation of the caspase cascade in three of four cutaneous squamous cell carcinoma (SCC) cell lines, after treatment with diclofenac plus hyaluronic acid and diclofenac alone; one cell line remained nonresponsive. The effects were less pronounced in normal keratinocytes and cytotoxic effects were not seen. Detailed analysis of apoptosis pathways employed by diclofenac in these cells may help to improve therapeutic strategies and to overcome possible mechanisms that are involved in nonresponsiveness.

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Growth Stimulation and Epidermal Growth Factor Receptor Induction in Cyclooxygenase-Overexpressing Human Colon Carcinoma Cells

Cited by 27 publications

References 13 publications

Cyclooxygenase 2-Regulated Genes an Alternative Avenue to the Development of New Therapeutic Drugs for Colorectal Cancer

Cyclooxygenase 2-Regulated Genes an Alternative Avenue to the Development of New Therapeutic Drugs for Colorectal Cancer

Prostaglandins and Cancer

The role of apoptosis in therapy and prophylaxis of epithelial tumours by nonsteroidal anti-inflammatory drugs (NSAIDs)

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