EFFECTIVENESS OF COMBINED LIMONENE AND 4-HYDROXYANDROSTENEDIONE IN THE TREATMENT OF NMU-INDUCED RAT MAMMARY-TUMORS

Limonene, a monocyclic monoterpene, occurs naturally in orange peel oil. It has been shown to exhibit both chemopreventive and chemotherapeutic activity without toxicity in rodent models. In this study we examined the effect of limonene both al maximally optimal and suboptimal doses and in combination with suboptimal doses of 4-hydroxyandrostrenedione on nitrosmethylurea-induced rat mammary tumours. A 10% limonene dose mixed in the diet caused tumour regression in all animals. A 5% limonene dose was only able to cause regression in 50% of the rats (P<0.05). A suboptimal dose of 4-hydroxyandrostrenedione (12.5 mg kg(-1)) resulted in tumour regression in 75% of rats. A combination of 5% limonene with 4-hydroxyandrostrenedione (12.5 mg kg(-1)) resulted in a greater tumour regression (83.3%) than either agent given individually (P<0.001 and 0.006 for limonene/4-hydroxyandrostrenedione vs limonene alone and 4-hydroxyandrostrenedione alone respectively).