Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 May;69(5):879–882. doi: 10.1038/bjc.1994.170

Effectiveness of combined limonene and 4-hydroxyandrostenedione in the treatment of NMU-induced rat mammary tumours.

S K Chander 1, A G Lansdown 1, Y A Luqmani 1, J J Gomm 1, R C Coope 1, N Gould 1, R C Coombes 1
PMCID: PMC1968920  PMID: 8180018

Abstract

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 at 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.

Full text

PDF
879

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Coombes R. C., Goss P., Dowsett M., Gazet J. C., Brodie A. 4-Hydroxyandrostenedione in treatment of postmenopausal patients with advanced breast cancer. Lancet. 1984 Dec 1;2(8414):1237–1239. doi: 10.1016/s0140-6736(84)92795-8. [DOI] [PubMed] [Google Scholar]
  2. Crowell P. L., Chang R. R., Ren Z. B., Elson C. E., Gould M. N. Selective inhibition of isoprenylation of 21-26-kDa proteins by the anticarcinogen d-limonene and its metabolites. J Biol Chem. 1991 Sep 15;266(26):17679–17685. [PubMed] [Google Scholar]
  3. Elegbede J. A., Elson C. E., Qureshi A., Tanner M. A., Gould M. N. Inhibition of DMBA-induced mammary cancer by the monoterpene d-limonene. Carcinogenesis. 1984 May;5(5):661–664. doi: 10.1093/carcin/5.5.661. [DOI] [PubMed] [Google Scholar]
  4. Elegbede J. A., Elson C. E., Tanner M. A., Qureshi A., Gould M. N. Regression of rat primary mammary tumors following dietary d-limonene. J Natl Cancer Inst. 1986 Feb;76(2):323–325. [PubMed] [Google Scholar]
  5. Elson C. E., Maltzman T. H., Boston J. L., Tanner M. A., Gould M. N. Anti-carcinogenic activity of d-limonene during the initiation and promotion/progression stages of DMBA-induced rat mammary carcinogenesis. Carcinogenesis. 1988 Feb;9(2):331–332. doi: 10.1093/carcin/9.2.331. [DOI] [PubMed] [Google Scholar]
  6. Haag J. D., Lindstrom M. J., Gould M. N. Limonene-induced regression of mammary carcinomas. Cancer Res. 1992 Jul 15;52(14):4021–4026. [PubMed] [Google Scholar]
  7. Maltese W. A., Sheridan K. M., Repko E. M., Erdman R. A. Post-translational modification of low molecular mass GTP-binding proteins by isoprenoid. J Biol Chem. 1990 Feb 5;265(4):2148–2155. [PubMed] [Google Scholar]
  8. Maltzman T. H., Hurt L. M., Elson C. E., Tanner M. A., Gould M. N. The prevention of nitrosomethylurea-induced mammary tumors by d-limonene and orange oil. Carcinogenesis. 1989 Apr;10(4):781–783. doi: 10.1093/carcin/10.4.781. [DOI] [PubMed] [Google Scholar]
  9. Wattenberg L. W., Coccia J. B. Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone carcinogenesis in mice by D-limonene and citrus fruit oils. Carcinogenesis. 1991 Jan;12(1):115–117. doi: 10.1093/carcin/12.1.115. [DOI] [PubMed] [Google Scholar]
  10. Wattenberg L. W. Inhibition of neoplasia by minor dietary constituents. Cancer Res. 1983 May;43(5 Suppl):2448s–2453s. [PubMed] [Google Scholar]
  11. Wattenberg L. W., Sparnins V. L., Barany G. Inhibition of N-nitrosodiethylamine carcinogenesis in mice by naturally occurring organosulfur compounds and monoterpenes. Cancer Res. 1989 May 15;49(10):2689–2692. [PubMed] [Google Scholar]
  12. Wilkinson J. R., Williams J. C., Singh D., Goss P. E., Easton D., Coombes R. C. Response of nitrosomethylurea-induced rat mammary tumor to endocrine therapy and comparison with clinical response. Cancer Res. 1986 Sep;46(9):4862–4865. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES