Comparative Effects of Piroxicam and Esculetin on Incidence, Proliferation, and Cell Kinetics of Mammary Carcinomas Induced by 7,12-Dimethylbenz[a]anthracene in Rats on High- and Low-Fat Diets

Abstract

We investigated the effects of piroxicam, a cyclooxygenase inhibitor, and esculetin, a lipoxygenase inhibitor, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female rats. Seven days after receiving a 5-mg dose of DMBA, rats were fed either a high-fat (20% soybean oil) or low-fat (0.5% soybean oil) diet. One third of the rats received diets containing 0.01% piroxicam and one third received diets containing 0.03% esculetin. Esculetin significantly inhibited mammary tumorigenesis and tumor proliferation in the rats fed the high-fat and the low-fat diets. Piroxicam had no inhibitory effect. Our findings indicate that DMBA-induced mammary tumorigenesis is affected by lipoxygenase products rather than by cyclooxygenase products.

Inhibitory Effects of Nabumetone, a Cyclooxygenase‐2 Inhibitor, and Esculetin, a Lipoxygenase Inhibitor, on N‐Methyl‐N‐nitrosourea‐induced Mammary Carcinogenesis in Rats

“…However, Kitagawa and Noguchi found that piroxicam, one of the NSAIDs, had no inhibitory effect on DMBA-induced mammary carcinogenesis. 24) Usual NSAIDs inhibit both COX-1 and -2, and induce stomach ulcers and renal dysfunction as side effects. Recently, selective COX-2 inhibitors, which have few side effects, have attracted the attention of many researchers.…”

“…24) We decided to compare the effects of nabumetone, a cyclooxygenase inhibitor, and esculetin, a lipoxygenase inhibitor. Though the carcinogen which we used, MNU, was different from the one they used, the results in this study were similar to theirs.…”

“…It was reported that esculetin inhibited cell proliferation of the TMT-801 rat mammary tumor cell line, 22) cell proliferation of MDA-MB-231 breast cancer cells in vitro and mammary tumorigenesis 23) and tumor proliferation in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female rats. 24) In this paper, we investigated the chemopreventive effects of nabumetone, a relatively selective COX-2 inhibitor, and esculetin, a lipoxygenase inhibitor, on N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in SpragueDawley (SD) rats.…”

Inhibitory Effect of Natural Coumarin Compounds, Esculetin and Esculin, on Oxidative DNA Damage and Formation of Aberrant Crypt Foci and Tumors Induced by 1,2-Dimethylhydrazine in Rat Colons

“…21) Furthermore, it has been reported that esculetin inhibits mammary carcinogenesis. 22,23) 1,2-Dimethylhydrazine (DMH) is an alkylating carcinogen that causes neoplastic changes in colonic mucosa at a level proportional to the quantity of methylated DNA adducts induced in colonic crypt cells.24) DMH-induced colon tumors are currently the most popular models in which to study the morphology, pathogenesis, prevention, and treatment of colorectal cancer.25) Aberrant crypt foci (ACF), first observed in the colonic mucosa of carcinogen-treated rodents, 26) are considered to be preneoplastic lesions, 27) since they are observed at high frequency in the colonic mucosa of patients with colon cancer 28) and rodents treated with colon carcinogens. …”

Chemical characterization by GC-MS and phytotoxic potential of non-polar and polar fractions of seeds of Dioteryx odorata (Aubl.) Willd. from Venezuelan regions

“…27,28 Another study showed that esculetin and esculin can protect biomolecules from oxidative damage generated in the initial process of carcinogenesis. 29,30 Thus, the mass fraction of seeds of D. odorata is a rich source of coumarin and esculin, showing high levels of concentration of these compounds. These compounds are consumed in the preparations of D. odorata, and although there is evidence of beneficial effects against cancer, they remain a potential source of harmful xenobiotics to humans.…”