Cyclooxygenase-2 inhibitors: what went wrong?

James, Michael J.; Cleland, Leslie G.

doi:10.1097/01.mco.0000214565.67439.83

Cited by 20 publications

(8 citation statements)

References 46 publications

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“…However, some recent studies have demonstrated that COX-2 specific inhibitors as well as conventional NSAIDs have potential side effects (Graham et al, 2002) and induce hypertension, a common management problem in cancer patients (Yancik et al, 1996). According to a recent report by James and Cleland (2006) selective COX-2 inhibitors can increase cardiovascular risks and thus are unsafe for clinical use. However, in our study, vitamin C showed a distinct effect on the suppression of COX-2 expression.…”

Section: Discussionmentioning

confidence: 98%

Vitamin C suppresses proliferation of the human melanoma cell SK‐MEL‐2 through the inhibition of cyclooxygenase‐2 (COX‐2) expression and the modulation of insulin‐like growth factor II (IGF‐II) production

Lee

Kang

Jung

et al. 2008

Journal Cellular Physiology

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Vitamin C plays a crucial role in the suppression of proliferation of several types of cancer. Over-expression of cyclooxygenase (COX)-2 and type I insulin-like growth factor (IGF) receptor are important for proliferation and protection from apoptosis in malignancies. However, its specific mechanisms, especially the interaction between COX-2 expression and IGF-I axis mediated by vitamin C, remain yet to be clarified. Therefore, we investigated the effects of vitamin C on the proliferation of melanoma cells via the modulation of COX-2 expression and IGF-I axis. As a result, we found that 1.0 mM vitamin C inhibits the proliferation of SK-MEL-2 without induction of apoptosis. At that moment, IGF-II production was decreased, followed by the inhibition of COX-2 activity. IGF-IR expression was also down-regulated by vitamin C treatment. It coincided with the result from the inhibition of COX-2 by NS-398 and COX-2 siRNA. In addition, the decreased IGF-IR expression by vitamin C was restored by the treatment of recombinant prostaglandin E2. Finally, we determined whether the signal pathway would be involved in vitamin C-induced IGF-II and IGF-IR down-regulation. When the cells were exposed to SB203580, a specific inhibitor of p38 MAPK, COX-2 expression was dramatically recovered. In addition, phosphorylated p38 MAPK was increased after vitamin C treatment. Taken together, vitamin C suppresses proliferation of the human melanoma cell line SK-MEL2 via the down-regulation of IGF-II production and IGF-IR expression, which is followed by the activation of p38 MAPK and the inhibition of COX-2 expression.

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Section: Discussionmentioning

confidence: 98%

Vitamin C suppresses proliferation of the human melanoma cell SK‐MEL‐2 through the inhibition of cyclooxygenase‐2 (COX‐2) expression and the modulation of insulin‐like growth factor II (IGF‐II) production

Lee

Kang

Jung

et al. 2008

Journal Cellular Physiology

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“…While the risk profile that lead to the withdrawal of rofecoxib might be indicative of aCOX-2 class effect [11,19,55], this may not have been the understanding of many prescribers (or consumers) for this group of community living older Australian women. This interpretation of COX-2 class risk has also varied across international studies of prescribing following the rofecoxib discrediting event, with some studies demonstrating a prescriber response to a class effect [2,23,26,28,30], and some not [22,24,26].…”

Section: Discussionmentioning

confidence: 99%

An observational study of the discrediting of COX-2 NSAIDs in Australia: Vioxx or class effect?

et al. 2011

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BackgroundWhen a medicine such as rofecoxib (Vioxx) is withdrawn, or a whole class of medicines discredited such as the selective COX-2 inhibitors (COX-2s), follow-up of impacts at consumer level can be difficult and costly. The Australian Longitudinal Study on Women's Health provides a rare opportunity to examine individual consumer medicine use following a major discrediting event, the withdrawal of rofecoxib and issuing of safety warnings on the COX-2 class of medicines. The overall objective of this paper was to examine the impact of this discrediting event on dispensing of the COX-2 class of medicines, by describing medicine switching behaviours of older Australian women using rofecoxib in September 2004; the uptake of other COX-2s; and the characteristics of women who continued using a COX-2.MethodsParticipants were concessional beneficiary status women from the Older cohort (born 1921-26) of the Australian Longitudinal Study on Women's Health who consented to linkage to Pharmaceutical Benefits Scheme data, with at least one rofecoxib prescription dispensed in the 12 months before rofecoxib withdrawal. A prescription was defined as one dispensing occasion. Women were grouped by rofecoxib pattern of use: continuous (nine or more prescriptions dispensed in the 12 months prior to rofecoxib withdrawal) or non-continuous (eight or less prescriptions dispensed in the 12 months prior to rofecoxib withdrawal) users. Incidence rate per 100,000 person days and incidence risk ratio described uptake of alternate medicines, following rofecoxib withdrawal. Kaplan-Meier curves described differences in uptake patterns by medicine and pattern of rofecoxib use. Patterns of use of COX-2s in the next 100 days after first COX-2 uptake were described.ResultsMedicine switches and pattern of medicines uptake differed significantly depending upon whether a woman was a continuous or non-continuous rofecoxib user prior to rofecoxib discrediting. Continuous rofecoxib users overwhelmingly switched to another COX-2 and remained continuing COX-2 users for at least 100 days post-switch.ConclusionsThe typical switching behaviour of this group of women suggests that the issues leading to the discrediting of rofecoxib were not seen as a COX-2 class effect by prescribers to this high use group of consumers.

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“…They note that maternal ingestion of nimuselide, a coxib, may cause kidney failure in the unborn child. James and Cleland (2006) present other telling points against the use of coxibs. For example, the pharmaceutical company marketing rofecoxib denounced clinical trial evidence showing that the drug increases cardiovascular risk, and prescriptions of celecoxib have been common despite the lack of improved upper gastrointestinal safety.…”

Section: Nsaids and Antacidsmentioning

confidence: 95%

Diets and Circadian Rhythms: Challenges from Biology for Medicine

Steen

2006

Acta Biotheor

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Autoimmune diseases such as rheumatoid arthritis and gastrointestinal disorders such as stomach ulcers are often treated with drugs. NSAIDs, a common treatment in rheumatoid arthritis, may cause stomach ulcers which call for additional medications, notably antacids in the sense of drugs that suppress acid secretion by the stomach. Infection with Helicobacter pylori also plays a role in the ulcers. The infection is typically treated with antibiotics added to antacids. Considering NSAIDs and antacids, we suspect that overmedication is common to the extent that particular diets are a better option. Current research and current treatments with these drugs are also problematic since circadian rhythms are mostly disregarded. All the processes involved in the disorders treated show marked variations in the course of the day. Hence experiments conforming to the guidelines of evidence-based medicine, and treatments in line with them, have outcomes strongly depending on the time factor. This calls for reforms in medicine with fresh inputs from biology.

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Cyclooxygenase-2 inhibitors: what went wrong?

Abstract: These events provide a case study of a failure of the medical journal literature to guide drug usage.

Cited by 20 publications

References 46 publications

Vitamin C suppresses proliferation of the human melanoma cell SK‐MEL‐2 through the inhibition of cyclooxygenase‐2 (COX‐2) expression and the modulation of insulin‐like growth factor II (IGF‐II) production

Vitamin C suppresses proliferation of the human melanoma cell SK‐MEL‐2 through the inhibition of cyclooxygenase‐2 (COX‐2) expression and the modulation of insulin‐like growth factor II (IGF‐II) production

An observational study of the discrediting of COX-2 NSAIDs in Australia: Vioxx or class effect?

Diets and Circadian Rhythms: Challenges from Biology for Medicine

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