Induction of Apoptosis by Celecoxib in Cell Culture: An Uncertain Role for Cyclooxygenase-2

Schönthal, Axel H.

doi:10.1158/0008-5472.can-06-3414

Cited by 10 publications

(6 citation statements)

References 5 publications

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“…On one hand, there is clear evidence that COX-2 is an important player even in advanced tumours, where a constellation of other cellular components, such as activated oncogenes and inactivated tumour suppressors, has usurped growth control and drives the malignant expansion. On the other hand, there are an increasing number of reports indicating that celecoxib does not require the presence of COX-2 in order to exert its antitumour activities (Kashfi and Rigas, 2005;Grösch et al, 2006;Schönthal, 2007). Even more striking, it was demonstrated that close structural analogues of celecoxib -devoid of any COX-2 inhibitory activity -were able to potently mimic all antitumour properties of celecoxib investigated so far, not just in vitro but also in various xenograft animal tumour models in vivo Kulp et al, 2004;Schönthal, 2006).…”

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confidence: 99%

Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy

Schönthal

2007

Br J Cancer

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Celecoxib (Celebrex s ) was developed as a selective cyclooxygenase-2 (COX-2) inhibitor for the treatment of chronic pain. However, it now appears that this compound harbours additional pharmacologic activities that are entirely independent of its COX-2-inhibitory activity. This review presents the recently emerged direct non-COX-2 targets of celecoxib and their proposed role in mediating this drug's antitumour effects.

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confidence: 99%

Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy

Schönthal

2007

Br J Cancer

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“…Likewise, coxibs bind to the transmembrane protein SERCA ( 45 – 47 ), a pump that can induce cellular apoptosis by increasing the intracellular calcium concentration. These different pro-apoptotic and anti-oncogenic targets have been confirmed by an increasing number of reports indicating that celecoxib does not require the presence of COX-2 to exert its anti-tumoral activity ( 44 , 48 , 49 ). Even more striking, it has been shown that structural analogs close to celecoxib, devoid of any COX-2 inhibitory activity, were able to mimic the anti-tumor properties of celecoxib studied so far, not only in vitro but also in various in vivo xenograft models ( 43 , 50 , 51 ).…”

Section: Discussionmentioning

confidence: 70%

Development of PET Radioligands Targeting COX-2 for Colorectal Cancer Staging, a Review of in vitro and Preclinical Imaging Studies

et al. 2021

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Colorectal cancer (CRC) is the second most common cause of cancer death, making early diagnosis a major public health challenge. The role of inflammation in tumorigenesis has been extensively explored, and among the identified markers of inflammation, cyclooxygenase-2 (COX-2) expression seems to be linked to lesions with a poor prognosis. Until now, COX-2 expression could only be accessed by invasive methods, mainly by biopsy. Imaging techniques such as functional Positron Emission Tomography (PET) could give access to in vivo COX-2 expression. This could make the staging of the disease more accurate and would be of particular interest in the exploration of the first metastatic stages. In this paper, we review recent progress in the development of COX-2 specific PET tracers by comparing the radioligands' characteristics and highlighting the obstacles that remain to be overcome in order to achieve the clinical development of such a radiotracer, and its evaluation in the management of CRC.

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“…The question remains as to whether the effects of selective COX-2 inhibitors occur in a COX-2 expression-dependent or independent manner in tumor cells [ 21 , 22 , 23 , 24 , 25 , 26 ]. For example, many reports indicate that the COX-2 selective inhibitor celecoxib does not require the presence of COX-2 to implement its anti-tumor effects [ 22 , 25 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

CRISPR/Cas9 Mediated Knockout of Cyclooxygenase-2 Gene Inhibits Invasiveness in A2058 Melanoma Cells

Haase-Kohn

Laube

Donat

et al. 2022

Cells

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The inducible isoenzyme cyclooxygenase-2 (COX-2) is an important hub in cellular signaling, which contributes to tumor progression by modulating and enhancing a pro-inflammatory tumor microenvironment, tumor growth, apoptosis resistance, angiogenesis and metastasis. In order to understand the role of COX-2 expression in melanoma, we investigated the functional knockout effect of COX-2 in A2058 human melanoma cells. COX-2 knockout was validated by Western blot and flow cytometry analysis. When comparing COX-2 knockout cells to controls, we observed significantly reduced invasion, colony and spheroid formation potential in cell monolayers and three-dimensional models in vitro, and significantly reduced tumor development in xenograft mouse models in vivo. Moreover, COX-2 knockout alters the metabolic activity of cells under normoxia and experimental hypoxia as demonstrated by using the radiotracers [18F]FDG and [18F]FMISO. Finally, a pilot protein array analysis in COX-2 knockout cells verified significantly altered downstream signaling pathways that can be linked to cellular and molecular mechanisms of cancer metastasis closely related to the enzyme. Given the complexity of the signaling pathways and the multifaceted role of COX-2, targeted suppression of COX-2 in melanoma cells, in combination with modulation of related signaling pathways, appears to be a promising therapeutic approach.

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Induction of Apoptosis by Celecoxib in Cell Culture: An Uncertain Role for Cyclooxygenase-2

Cited by 10 publications

References 5 publications

Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy

Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy

Development of PET Radioligands Targeting COX-2 for Colorectal Cancer Staging, a Review of in vitro and Preclinical Imaging Studies

CRISPR/Cas9 Mediated Knockout of Cyclooxygenase-2 Gene Inhibits Invasiveness in A2058 Melanoma Cells

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