Selective Cyclooxygenase‐2 Inhibition: A Target in Cancer Prevention and Treatment

Subongkot, Suphat; Frame, David; Leslie, William R.; Drajer, Deborah

doi:10.1592/phco.23.1.9.31916

Cited by 47 publications

(38 citation statements)

References 147 publications

(211 reference statements)

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“…In another study, investigators have demonstrated that in nonsmall-cell lung cancer cell lines, the selective COX-2 inhibitors could also enhance the cytotoxicity of various anticancer agents [23] . Thus it is expected that the potentially synergistic combination of COX-2 inhibitors and chemotherapy will play an important role in the future treatment of colorectal cancer [24] . However, in 2000, the VIGOR study had suggested a signifi cantly increased risk of acute myocardial infarction when taking another COX-2 inhibitor, rofecoxib (trade names Vioxx, Ceoxx and Ceeoxx) [25] .…”

Section: Discussionmentioning

confidence: 99%

Synergistic Inhibitory Effects of Curcumin and 5-Fluorouracil on the Growth of the Human Colon Cancer Cell Line HT-29

Jiang²,

Xia³

et al. 2005

Chemotherapy

127

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The synergistic effect of combination treatment with COX-2 inhibitors and chemotherapy may be another promising therapy regimen in the future treatment of colorectal cancer. Curcumin, a major yellow pigment in turmeric which is used widely allover the world, inhibits the growth of human colon cancer cell line HT-29 significantly and specifically inhibits the expression of COX-2 protein. However, the worldwide exposure of populations to curcumin raised the question of whether this agent would enhance or inhibit the effects of chemotherapy. In this report, we evaluated the growth-inhibitory effect of curcumin and a traditional chemotherapy agent, 5-FU, against the proliferation of a human colon cancer cell line (HT-29). The combination effect was quantitatively determined using the method of median-effect principle and the combination index. The inhibition of COX-2 expression after treatment with the curcumin-5-FU combination was also evaluated by Western blot analysis. The IC₅₀ value in the HT-29 cells for curcumin was 15.9 ± 1.96 µM and for 5-FU it was 17.3 ± 1.85 µM. When curcumin and 5-FU were used concurrently, synergistic inhibition of growth was quantitatively demonstrated. The level of COX-2 protein expression was reduced almost 6-fold after the combination treatment. Our results demonstrate synergism between curcumin and 5-FU at higher doses against the human colon cancer cell line HT-29. This synergism was associated with the decreased expression of COX-2 protein.

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Section: Discussionmentioning

confidence: 99%

Synergistic Inhibitory Effects of Curcumin and 5-Fluorouracil on the Growth of the Human Colon Cancer Cell Line HT-29

Jiang²,

Xia³

et al. 2005

Chemotherapy

127

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“…Decreased cancer risk may be attributable to NSAID-related inhibition of cyclooxygenase-2 (COX-2) expression and subsequent prostaglandin synthesis, enhancement of cellular immune response, or induction of apoptosis (17)(18)(19)(20). There have been few studies that address the role of analgesics in the chemoprevention of endometrial cancer.…”

Section: Introductionmentioning

confidence: 99%

Regular Analgesic Use and Risk of Endometrial Cancer

Moysich¹,

Baker²,

Rodabaugh

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Analgesic use has been implicated in the chemoprevention of a number of solid tumors, but thus far, no previous research has focused on the role of aspirin in endometrial cancer etiology. Methods: We conducted a hospital-based case-control study of 427 women with primary, incident endometrial cancer, and 427 age-and residence-matched controls without benign or malignant neoplasms. All participants received medical services at Roswell Park Cancer Institute in Buffalo, NY, and completed a comprehensive epidemiologic questionnaire. Women who reported analgesic use at least once a week for at least 6 months were classified as regular users and served as the reference group throughout the analyses. We used unconditional logistic regression analyses to compute crude and adjusted odds ratios (OR) with corresponding 95% confidence intervals (CI). Results: Compared with nonusers, regular aspirin users were

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“…The tumorpromoting activities of COX-2 and its prostaglandins are mediated via several mechanisms, including conversion of procarcinogens to carcinogens, stimulation of tumor cell growth, prevention of apoptotic cell death, promotion of angiogenesis and immunosuppression (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Several reviews have summarized evidence that nonsteroidal antiinflammatory drugs (NSAID) and, in particular, selective COX-2 inhibitors, are potentially interesting in cancer therapy (2)(3)(4)(5)(6)11). However, the enthusiasm was recently hampered by evidence of cardiovascular side effects (increase in the incidence of myocardial infarction) when using COX-2 inhibitors during longterm treatments (12).…”

Section: Introductionmentioning

confidence: 99%

Tumor Radiosensitization by Antiinflammatory Drugs: Evidence for a New Mechanism Involving the Oxygen Effect

et al. 2005

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We hypothesized that nonsteroidal antiinflammatory drugs (NSAIDs) might enhance tumor radiosensitivity by increasing tumor oxygenation (pO 2 ), via either a decrease in the recruitment of macrophages or from inhibition of mitochondrial respiration. The effect of four NSAIDs (diclofenac, indomethacin, piroxicam, and NS-398) on pO 2 was studied in murine TLT liver tumors and FSaII fibrosarcomas. At the time of maximum pO 2 (t max , 30 minutes after administration), perfusion, oxygen consumption, and radiation sensitivity were studied. Local pO 2 measurements were done using electron paramagnetic resonance. Tumor perfusion and permeability measurements were assessed by dynamic contrast-enhanced magnetic resonance imaging. The oxygen consumption rate of tumor cells after in vivo NSAID administration was measured using high-frequency electron paramagnetic resonance. Tumor-infiltrating macrophage localization was done with immunohistochemistry using CD11b antibody. All the NSAIDs tested caused a rapid increase in pO 2 . At t max , tumor perfusion decreased, indicating that the increase in pO 2 was not caused by an increase in oxygen supply. Also at t max , global oxygen consumption decreased but the amount of tumor-infiltrating macrophages remained unchanged. Our study strongly indicates that the oxygen effect caused by NSAIDs is primarily mediated by an effect on mitochondrial respiration. When irradiation (18 Gy) was applied at t max , the tumor radiosensitivity was enhanced (regrowth delay increased by a factor of 1.7). These results show the potential utility of an acute administration of NSAIDs for radiosensitizing tumors, and shed new light on the mechanisms of NSAID radiosensitization. These results also provide a new rationale for the treatment schedule when combining NSAIDs and radiotherapy. (Cancer Res 2005; 65(17): 7911-6)

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Selective Cyclooxygenase‐2 Inhibition: A Target in Cancer Prevention and Treatment

Cited by 47 publications

References 147 publications

Synergistic Inhibitory Effects of Curcumin and 5-Fluorouracil on the Growth of the Human Colon Cancer Cell Line HT-29

Synergistic Inhibitory Effects of Curcumin and 5-Fluorouracil on the Growth of the Human Colon Cancer Cell Line HT-29

Regular Analgesic Use and Risk of Endometrial Cancer

Tumor Radiosensitization by Antiinflammatory Drugs: Evidence for a New Mechanism Involving the Oxygen Effect

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