Research in this laboratory has shown that some citrus limonoids can inhibit the development of 7,12-dimethylbenz[a]anthracene-induced oral tumors. The data from these studies have suggested that certain rings in the limonoid nucleus may be critical to antineoplastic activity. Using the hamster cheek pouch model, three new limonoids (ichangensin, deoxylimonin, and obacunone) have now been tested for cancer chemopreventive activity. In the first experiment, it was found that the treatments with ichangensin had no effect on tumor number or burden. In the second experiment, obacunone reduced tumor number and burden by 25 and 40%, respectively, whereas deoxylimonin reduced tumor number and burden by 30 and 50%, respectively. The results with deoxylimonin were significant, p < 0.05. Overall, the data indicated that changes in the A ring of the limonoid nucleus can lead to a loss of anticancer activity, whereas changes in the D ring can be tolerated without any apparent loss of biological activity.

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.

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