INHIBITION OF CHEMICALLY-INDUCED CARCINOGENESIS BY CITRUS LIMONOIDS

Limonin and nomilin are two of the bitter principles found in citrus fruits such as lemon, lime, orange and grapefruit. Both citrus limonoids have been found to induce increased activity of the detoxifying enzyme glutathione S-transferase. The increased enzyme activity was correlated with the ability of these compounds to inhibit chemically induced carcinogenesis in laboratory animals. Administration of nomilin by gavage to ICR/Ha mice reduced the incidence and number of forestomach tumors per mouse induced by benzo[a]pyrene (BP). Addition of nomilin and limonin to the diet at various concentrations inhibited BP-induced lung tumor formation in A/J mice. The inhibition of lung tumors was correlated with inhibition of the formation of BP-DNA adducts in the lung. Topical application of the limonoids was found to inhibit both the initiation and the promotion phases of carcinogenesis in the skin of SENCAR mice. Nomilin appeared to be more effective during the initiation stage while limonin was more potent as an inhibitor during the promotion phase of carcinogenesis. These findings suggest citrus limonoids may be useful as cancer chemopreventive agents.