Celecoxib exerts antitumor effects in canine mammary tumor cells via COX-2-independent mechanisms

Tamura, Dai; Saito, Tetsuichiro; Murata, Kanae; Kawashima, Masafumi; Asano, Ryuji

doi:10.3892/ijo.2015.2820

Cited by 17 publications

(11 citation statements)

References 48 publications

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“…Another clinically feasible approach to interfere with the drug-induced overexpression of Pgp may rely on the inhibition of COX-2. Selective COX-2 inhibitors (i.e., celecoxib, firocoxib, or meloxicam) have pro-apoptotic and anti-proliferative effects in human and canine tumors [67][68][69][70]. Interestingly, Pgp was shown to mediate celecoxib-induced apoptosis by activating caspase-3 and increasing cytochrome c release from the mitochondria [71].…”

Section: Discussionmentioning

confidence: 99%

Celecoxib Prevents Doxorubicin-Induced Multidrug Resistance in Canine and Mouse Lymphoma Cell Lines

Karai

Szebényi

Windt

et al. 2020

Cancers

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Background: Treatment of malignancies is still a major challenge in human and canine cancer, mostly due to the emergence of multidrug resistance (MDR). One of the main contributors of MDR is the overexpression P-glycoprotein (Pgp), which recognizes and extrudes various chemotherapeutics from cancer cells. Methods: To study mechanisms underlying the development of drug resistance, we established an in vitro treatment protocol to rapidly induce Pgp-mediated MDR in cancer cells. Based on a clinical observation showing that a 33-day-long, unplanned drug holiday can reverse the MDR phenotype of a canine diffuse large B-cell lymphoma patient, our aim was to use the established assay to prevent the emergence of drug resistance in the early stages of treatment. Results: We showed that an in vitro drug holiday results in the decrease of Pgp expression in MDR cell lines. Surprisingly, celecoxib, a known COX-2 inhibitor, prevented the emergence of drug-induced MDR in murine and canine lymphoma cell lines. Conclusions: Our findings suggest that celecoxib could significantly improve the efficiency of chemotherapy by preventing the development of MDR in B-cell lymphoma.

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Section: Discussionmentioning

confidence: 99%

Celecoxib Prevents Doxorubicin-Induced Multidrug Resistance in Canine and Mouse Lymphoma Cell Lines

Karai

Szebényi

Windt

et al. 2020

Cancers

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“…After 24 and 48 h incubation, supernatants were removed and centrifuged at 1,000 × g for 10 min. The amount of PGE2 was determined using the Prostaglandin E 2 ELISA kit-Monoclonal from Cayman Chemical Company (Ann Arbor, MI, USA) according the manufacturer's protocol as previously described (31). …”

Section: Methodsmentioning

confidence: 99%

Meloxicam decreases the migration and invasion of CF41.Mg canine mammary carcinoma cells

et al. 2017

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Cyclooxygenase (COX)-2 expression is positively correlated with malignant features in canine mammary carcinomas. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX activity and may therefore possess anticancer effects. Meloxicam is an NSAID that is widely used in human and veterinary medicine. High concentrations of meloxicam have been reported to be antitumorigenic in vitro; however, the effect of meloxicam at concentrations that are equivalent to those that can be obtained in vivo remains unknown. In the current study, the in vitro effects of low-dose meloxicam (0.25 µg/ml) on CF41.Mg canine mammary carcinoma cells were evaluated. The effects on cell proliferation, apoptosis, cell migration and invasion, in addition to the expression of different molecules associated with tumor invasiveness were analyzed. No effect on cell viability and apoptosis were observed. However, cell migration and invasion were significantly reduced following treatment with meloxicam. MMP-2 expression and activity were similarly reduced, explaining the impaired cell invasion. In addition, β-catenin expression was downregulated, while its phosphorylation increased. These results indicate that 0.25 µg/ml meloxicam reduces cell migration and invasion, in part through modulating MMP-2 and β-catenin expression. Additional studies are required to elucidate the mechanism associated with the anti-invasive effect of meloxicam on CF41.Mg cells. The results of the present study suggest that meloxicam has a potential adjunctive therapeutic application, which could be useful in controlling the invasion and metastasis of canine mammary carcinomas.

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“…Celecoxib is a commonly used COX‐2‐selective NSAID in humans for treatment of OA and has a higher safety profile for the gastrointestinal tract 66 . Few studies have evaluated the use of systemic celecoxib in veterinary medicine, and of those performed, a majority have occurred in dogs 67‐69 . In an experimental model of OA in dogs, gross and histologic cartilage damage, macroscopic synovial inflammation and proteoglycan turnover were not different between celecoxib‐treated and control groups despite lower synovial PGE2 in the celecoxib‐treated group 68 .…”

Section: Assessment Of the Future Management Of Pain And Inflammation...mentioning

confidence: 99%

Non‐steroidal anti‐inflammatory drugs in equine orthopaedics

Jacobs

Schnabel

McIlwraith

et al. 2022

Equine Veterinary Journal

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Orthopaedic disorders are one of the most common complaints that will be managed by the equine practitioner and one which plays a significant role in the loss of use and wastage of horses within multiple equine disciplines. [1][2][3][4][5] Orthopaedic disease can be acute or chronic, is accompanied by inflammation and often manifests as lameness. Following injury or disruption to one or multiple musculoskeletal tissues, the inflammatory cascade is activated, leading to local increased recruitment of proinflammatory cells that release an array of cytokines and prostanoids. Production of prostanoids, importantly prostaglandin E2 (PGE2), through metabolism of arachidonic acid by cyclooxygenase (COX), is an important component of the inflammatory reaction. Prostanoids contribute to pain and hyperalgesia by increasing the sensitivity for signalling by peripheral nociceptive terminals. 6 Tissue injury also stimulates release of neurotransmitters from central terminals of nociceptors and augments production of PGE2 in the spinal cord. This leads to additional excitation and disinhibition of dorsal horn neurons and generates abnormal responses to sensory signals from the periphery. 7One of the main goals in management of orthopaedic disease in horses is reduction of inflammation and, as a result, reduction in associated pain and lameness. Another goal is to minimise disease progression and long-term deterioration of tissues.Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most readily available and cost-effective methods to inhibit the inflammatory response and, as a result, these drugs continue to be a mainstay of management of equine orthopaedic injury and lameness. In cases of acute orthopaedic disease, such as septic arthritis, NSAIDs are important in blunting the initial inflammatory response in order to decrease pain and to prevent further propagation of inflammation. These drugs also play important roles in modulating chronic disease, such as that seen with osteoarthritis (OA), by controlling persistent inflammation and slowing the progression of disease. Clinicians need to be cognisant of the potential gastrointestinal and renal side effects associated with the administration of NSAIDs.Gastrointestinal effects include oral and gastric ulceration and right

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Celecoxib exerts antitumor effects in canine mammary tumor cells via COX-2-independent mechanisms

Cited by 17 publications

References 48 publications

Celecoxib Prevents Doxorubicin-Induced Multidrug Resistance in Canine and Mouse Lymphoma Cell Lines

Celecoxib Prevents Doxorubicin-Induced Multidrug Resistance in Canine and Mouse Lymphoma Cell Lines

Meloxicam decreases the migration and invasion of CF41.Mg canine mammary carcinoma cells

Non‐steroidal anti‐inflammatory drugs in equine orthopaedics

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