The effects of citrus limonoids on hamster buccal pouch carcinogenesis

Abstract

Two citrus limonoids, limonin and nomilin, were tested for their effects on the development of 7,12-dimethylbenz[a]anthracene (DMBA)-induced buccal pouch epidermoid carcinomas. Forty-five female Syrian hamsters were divided into three equal groups. The left buccal pouches of the animals in each group were pretreated topically with two applications of dimethylsulfoxide (DMSO) (group I), a 2.5% solution of limonin dissolved in DMSO (group II) or a 2.5% solution of nomilin dissolved in DMSO (group III). After this initial treatment, 11 hamsters from each group were selected. The left buccal pouches of these animals were painted 2 or 3 times weekly with a 0.5% solution of DMBA in mineral oil. On alternate days the pouches were painted with DMSO (I), the 2.5% solution of limonin (II) or the 2.5% solution of nomilin (III). The 12 remaining hamsters were used as controls and were painted with mineral oil and DMSO (I), mineral oil and the 2.5% solution of limonin (II), or mineral oil and the 2.5% solution of nomilin (III). After 15 weeks the hamsters were killed, the pouches were excised and the tumors were counted and measured. Tumors of variable size were common in the animals treated with DMBA. However, the animals receiving topical applications of limonin exhibited a 60% reduction in tumor burden. Further comparisons between groups I and II showed that this reduction in tumor burden was due to a 20% decrease in tumor number and a 50% decrease in tumor mass. The results for group III showed that nomilin was considerably less effective as an inhibitor of DMBA-induced neoplasia.

Limonin Bitterness in Citrus Juices

“…Aglycones have been more intensely investigated than the glucosides. Particularly, the two most abundant limonoids in citrus, limonin and nomilin, have been found to inhibit chemically induced carcinogenesis in mice and hamsters (Miller et al, 1989). Their inhibitory potential appears to correlate with their ability to induce the detoxifying enzyme, glutathione S-transferase (Lam et aI., 1989).…”

“…In addition to contributing to the bitter constituents in citrus juices, citrus limonoids possess anticarcinogenic activity in laboratory animals Miller et al, 1989Miller et al, , 1992 and cultured human breast cancer cells (Guthrie et al, 1997(Guthrie et al, , 1998. Evidence suggests that some of the anticancer properties of these compounds are due to induction of the detoxifying enzyme, glutathione S-transferase activity .…”

Potential Health Benefits of Citrus: An Overview

“…Nomilin proved to be more effective during the initiation stage of carcinogenesis, and limonin was more effective during the promotional stage of carcinogenesis. In the hamster cheek pouch model for DMBA-induced oral tumors 13 limonoids, 12 naturally occurring and one synthetic limonoid, were tested for anticancer activity (24,(30)(31)(32)(33). Unlike the earlier work on insect antifeedant activity (16,17), the data showed that major changes could be made to the D ring of the limonoid nucleus without any apparent loss of anticancer activity.…”

Limonoids in Seeds of Iyo Tangor (Citrus iyo hort. ex Tanaka)

“…Citrus limonoids, however, have been shown to have biological activities. They induce increased activity of a detoxifying enzyme, glutathione Stransferase, and inhibit the formation of tumors in laboratory animals Miller et al, 1989).…”