Growth arrest of DMBA-induced mammary carcinogenesis with ibuprofen treatment in female Sprague-Dawley rats

Joarder, Farahnaz S.; Abou-Issa, Hussein; Robertson, Fredika M.; Parrett, Michelle L.; Alshafie, Galal A.; Harris, Randall E.

doi:10.3892/or.4.6.1271

Cited by 9 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4 -6 Furthermore, examination of several NSAIDs in chemoprevention models of breast cancer in rodents indicate that NSAIDs can prevent the development of breast cancer if given at the time of carcinogen administration. 15,16 NSAIDs have, as a principle action, inhibition of prostaglandin synthesis, suggesting that prostaglandin metabolism contributes to early cancer development. More recently, inhibition of carcinogenesis has been achieved with NSAID derivatives that no longer inhibit cyclooxygenase, suggesting that protection may not be solely attributable to inhibited prostaglandin synthesis.…”

Section: Discussionmentioning

confidence: 99%

Increased cyclooxygenase-2 (cox-2) expression and activity in a murine model of metastatic breast cancer

et al. 2001

View full text Add to dashboard Cite

Elevated prostaglandin E 2 (PGE 2 ) production is a common feature of human malignancies. This activity has often been attributed to increased metabolic activity of the cyclooxygenase enzymes, although a direct comparison of these 2 parameters i.e., prostaglandin production and cox protein expression, is rarely performed in the same malignant tissue. Using a murine model of metastatic breast cancer, we show that PGE 2 levels are positively correlated with increased tumorigenic and metastatic potential. Because prostaglandin synthesis is a product of 2 isoforms of the cyclooxygenase enzyme, we examined the expression and activity of both isoforms. All tumor cell lines examined, regardless of phenotype, express both cox-1 and cox-2 proteins in vitro. In contrast to the uniform cox-2 expression in vitro, only tumors resulting from the transplantation of metastatic cell lines express cox-2 in vivo. Cox-1 is detected in both metastatic and nonmetastatic tumors. Thus, this is the first evidence that, in the tumor milieu, cox-2 expression can be regulated differently in metastatic vs. nonmetastatic lesions. Examination of PGE 2 synthesis in vitro reveals that nearly complete inhibition of prostaglandin synthesis occurs in the presence of either indomethacin, which inhibits both isoforms, or NS398, which is selective for the cox-2 isoform. Thus, even though cell lines express both isoforms, the majority of the prostaglandin synthesis stems from the activity of the inducible, cox-2 isoform. Likewise, cell growth is inhibited by both indomethacin and NS398 in a dose-dependent manner, albeit at higher drug concentrations than required to ablate PGE 2 synthesis. Despite the inhibition of prostaglandin synthesis, the cox-2 enzyme levels (protein and mRNA) were increased by either indomethacin or NS398. © 2001 Wiley-Liss, Inc. Key words: cyclooxygenase; prostaglandin; breast cancer; metastasisHigh cyclooxygenase activity is a common feature of human epithelial malignancies, 1,2 however, the biological significance of this metabolic activity has never been established. Recent epidemiologic studies have indicated that prolonged use of nonsteroidal antiinflammatory drugs (NSAIDs) is associated with a decreased risk of several malignancies, most notably colorectal cancers. 3 More recently, similar relationships have been observed in lung, breast and other cancers as well. 4 -6 Because NSAIDs have, as a principle action, inhibition of cyclooxygenases, these findings suggest that prostaglandin synthesis contributes to the risk of developing primary malignancies.We sought evidence for a role of prostaglandin synthesis in late tumor progression, i.e., tumor metastasis. Using a murine model of human breast cancer, we showed that higher prostaglandin E 2 (PGE 2 ) levels were observed in malignant mammary tissue in comparison to normal or premalignant gland. Furthermore, the highest PGE 2 levels were observed in the most malignant and metastatic tumors. 7 Two isoforms of cyclooxygenase (cox) are responsible for prostaglandin synthesis....

show abstract

Section: Discussionmentioning

confidence: 99%

Increased cyclooxygenase-2 (cox-2) expression and activity in a murine model of metastatic breast cancer

et al. 2001

View full text Add to dashboard Cite

show abstract

“…NSAIDs interfere with prostaglandin biosyntheses by inhibiting COX-1 and COX-2. Preclinical studies also indicate that COX inhibition may be useful in models of chemoprevention [7]. Thus, it will be important to test this hypothesis in vivo using COX-1 inhibitors that preferentially inhibit COX-1.…”

Section: Introductionmentioning

confidence: 99%

Effects of a selective cyclooxygenase-1 inhibitor in SKOV-3 ovarian carcinoma xenograft-bearing mice

Zhuo

et al. 2009

Med Oncol

View full text Add to dashboard Cite

To evaluate the effect of a cyclooxygenase-1 (COX-1) inhibitor, SC-560, on the growth inhibition of s.c. human ovarian SKOV-3 carcinoma and on angiogenesis. Human ovarian SKOV-3 carcinoma cells xenograft-bearing mice were treated with SC-560, a COX-1-selective inhibitor, 6 mg/kg alone i.g. daily, and i.p. injections of cisplatin 3 mg/kg every other day for 21 days. Prostaglandin E 2 (PGE 2 ) levels were determined by ELISA. Microvessel density (MVD) of ovarian carcinoma was determined with anti-CD 34 as the label by immunohistochemistry. In addition, the expression of COX-1 at protein levels in the control group was detected by immunohistochemistry. SC-560 reduced the growth of tumors when SKOV-3 cells were xenografted in nude female mice. The inhibitory rates in SC-560 group and cisplatin group were 47.1% and 51.7%, respectively, which is significant statistically compared to that of control group (all, P \ 0.05). In treatment groups, SC-560 significantly reduced intratumor PGE 2 levels (P \ 0.01). MVDs in SC-560 group were 35.73 ± 9.87, which are significant statistically compared to that of control group (74.33 ± 9.50) (P \ 0.01). COX-1, not COX-2, protein levels are elevated in tumor tissues. These findings may implicate COX-1 as a suitable target for the treatment of ovarian cancer and that antiangiogenic therapy can be used to inhibit ovarian cancer growth.

show abstract

“…Coxib use reduced the risk of breast cancer development by 71% (OR = 0.29, P < 0.01). Significant reductions in essential fatty acid, linolenic acid, had the opposite effect.In several subsequent preclinical investigations of chemically induced breast cancer, supplemental administration of general NSAIDs such as aspirin, ibuprofen, piroxicam, sulindac, and others, in the diet or drinking water consistently reduced the growth and progression of breast tumors [48][49][50] . The molecular basis for the antineoplastic effects of these general NSAIDS is linked to their inhibition of cyclooxgenase gene expression and enzyme activity.…”

mentioning

confidence: 99%

Cyclooxygenase-2 and the inflammogenesis of breast cancer

Harris

Casto

Harris

2014

WJCO

150

125

View full text Add to dashboard Cite

Cohesive scientific evidence from molecular, animal, and human investigations supports the hypothesis that constitutive overexpression of cyclooxygenase-2 (COX-2) is a ubiquitous driver of mammary carcinogenesis, and reciprocally, that COX-2 blockade has strong potential for breast cancer prevention and therapy. Key findings include the following: (1) COX-2 is constitutively expressed throughout breast cancer development and expression intensifies with stage at detection, cancer progression and metastasis; (2) essential features of mammary carcinogenesis (mutagenesis, mitogenesis, angiogenesis, reduced apoptosis, metastasis and immunosuppression) are linked to COX-2-driven prostaglandin E2 (PGE-2) biosynthesis; (3) upregulation of COX-2 and PGE-2 expression induces transcription of CYP-19 and aromatase-catalyzed estrogen biosynthesis which stimulates unbridled mitogenesis; (4) extrahepatic CYP-1B1 in mammary adipose tissue converts paracrine estrogen to carcinogenic quinones with mutagenic impact; and (5) agents that inhibit COX-2 reduce the risk of breast cancer in women without disease and reduce recurrence risk and mortality in women with breast cancer. Recent sharp increases in global breast cancer incidence and mortality are likely driven by chronic inflammation of mammary adipose and upregulation of COX-2 associated with the obesity pandemic. The totality of evidence clearly supports the supposition that mammary carcinogenesis often evolves as a progressive series of highly specific cellular and molecular changes in response to induction of constitutive overexpression of COX-2 and the prostaglandin cascade in the "inflammogenesis of breast cancer". Key words: Breast Cancer; Cyclooxygenase-2; Nonsteroidal anti-inflammatory drugs; Inflammogenesis; Estrogen; Aromatase Core tip: Mammary carcinogenesis often evolves as a series of highly specific cellular and molecular changes in response to induction of constitutive over-expression of cyclooxygenase-2 (COX-2) and the prostaglandin cascade; reciprocally, agents that block COX-2 have significant value in the chemoprevention and therapy of breast cancer.Harris RE, Casto BC, Harris ZM. Cyclooxygenase-2 and the inflammogenesis of breast cancer. World J Clin Oncol 2014; 5(4): 677-692 Available from: URL: http://www.wjgnet.com/2218-4333/full/v5/ i4/677.htm DOI: http://dx.doi.org/10.5306/wjco.v5.i4.677 INTRODUCTIONMore than a century ago, Virchow et al [1,2] chronic inflammation leads to cancer development by increasing cellular proliferation [3] . Various models of carcinogenesis have been proposed involving inflammatory stimuli and mediators of wound healing [4][5][6] . The recent discovery of the inducible cyclooxygenase-2 (COX-2) gene has rekindled interest in the causal link between inflammation and cancer, and various models of carcinogenesis have been proposed involving inflammatory stimuli and COX-2 expression [7][8][9][10] . The current review synthesizes and interprets the accumulating body of evidence supporting COX-2 driven inflammogenesis as a ge...

show abstract

Growth arrest of DMBA-induced mammary carcinogenesis with ibuprofen treatment in female Sprague-Dawley rats

Cited by 9 publications

References 0 publications

Increased cyclooxygenase-2 (cox-2) expression and activity in a murine model of metastatic breast cancer

Increased cyclooxygenase-2 (cox-2) expression and activity in a murine model of metastatic breast cancer

Effects of a selective cyclooxygenase-1 inhibitor in SKOV-3 ovarian carcinoma xenograft-bearing mice

Cyclooxygenase-2 and the inflammogenesis of breast cancer

Contact Info

Product

Resources

About