Phytochemistry Reviews

, Volume 14, Issue 1, pp 1–6 | Cite as

Recent developments in the bioactivity of mono- and diterpenes: anticancer and antimicrobial activity

  • Sara J. Greay
  • Katherine A. Hammer


Secondary plant metabolites, and in particular monoterpenes, have been recognised as potential medicinal agents for centuries. As such, terpenes have been the focus of a plethora of scientific studies examining various aspects of their bioactivity. In particular, antimicrobial activity and anticancer potential have been studied extensively. Whilst the antimicrobial and anticancer activity of terpenes has been demonstrated in vitro, fewer studies have been conducted examining specific aspects of the mechanisms of antimicrobial action and anticancer efficacy in vivo. The purpose of this review is therefore to examine recent advances in the areas of antimicrobial and anticancer activity.


Essential oil Tea tree oil Antibacterial Cytotoxicity Antitumour 



We thank Dr C. Locher (UWA) for providing the chemical structures. S. J. Greay and K. A. Hammer received financial support from Rural Industries Research and Development Corporation (RIRDC), Australia.


  1. Anderson L, Schmieder GJ, Werschler WP et al (2009) Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis. J Am Acad Dermatol 60:934–943CrossRefPubMedGoogle Scholar
  2. Bakkali F, Averbeck S, Averbeck D et al (2008) Biological effects of essential oils: a review. Food Chem Toxicol 46:446–475CrossRefPubMedGoogle Scholar
  3. Burt S (2004) Essential oils: their antibacterial properties and potential applications in foods: a review. Int J Food Microbiol 94:223–253CrossRefPubMedGoogle Scholar
  4. Calcabrini A, Stringaro A, Toccacieli L et al (2004) Terpinen-4-ol, the main component of Melaleuca alternifolia (tea tree) oil inhibits the in vitro growth of human melanoma cells. J Invest Dermatol 122:349–360CrossRefPubMedGoogle Scholar
  5. Carneiro de Barros J, Lúcia da Conceição M, Gomes Neto NJ et al (2009) Interference of Origanum vulgare L. essential oil on the growth and some physiological characteristics of Staphylococcus aureus strains isolated from foods. LWT Food Sci Technol 42:1139–1143CrossRefGoogle Scholar
  6. Challacombe JM, Suhrbier A, Parsons PG et al (2006) Neutrophils are a key component of the antitumor efficacy of topical chemotherapy with ingenol-3-angelate. J Immunol 177:8123–8132CrossRefPubMedGoogle Scholar
  7. Chaudhary SC, Alam MS, Siddiqui MS et al (2009) Perillyl alcohol attenuates Ras-ERK signaling to inhibit murine skin inflammation and tumorigenesis. Chem Biol Interact 179:145–153CrossRefPubMedGoogle Scholar
  8. Clark SS (2006) Perillyl alcohol induces c-Myc-dependent apoptosis in Bcr/Abl-transformed leukemia cells. Oncology 70:13–18CrossRefPubMedGoogle Scholar
  9. Cox SD, Mann CM, Markham JL et al (2000) The mode of antimicrobial action of the essential oil of Melaleuca alternifolia (tea tree oil). J Appl Microbiol 88:170–175CrossRefPubMedGoogle Scholar
  10. da Fonseca CO, Schwartsmann G, Fischer J et al (2008) Preliminary results from a phase I/II study of perillyl alcohol intranasal administration in adults with recurrent malignant gliomas. Surg Neurol 70:259–267CrossRefPubMedGoogle Scholar
  11. da Fonseca CO, Simao M, Lins IR et al (2010) Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma. J Cancer Res Clin Oncol 137:287–293CrossRefPubMedGoogle Scholar
  12. Devi KP, Nisha SA, Sakthivel R et al (2010) Eugenol (an essential oil of clove) acts as an antibacterial agent against Salmonella typhi by disrupting the cellular membrane. J Ethnopharmacol 130:107–115CrossRefPubMedGoogle Scholar
  13. Di Pasqua R, Mamone G, Ferranti P et al (2010) Changes in the proteome of Salmonella enterica serovar Thompson as stress adaptation to sublethal concentrations of thymol. Proteomics 10:1040–1049PubMedGoogle Scholar
  14. Echeverrigaray S, Michelim L, Delamare APL et al (2008) The effect of monoterpenes on swarming differentiation and haemolysin activity in Proteus mirabilis. Molecules 13:3107–3116CrossRefPubMedGoogle Scholar
  15. Elegbede JA, Flores R, Wang RC (2003) Perillyl alcohol and perillaldehyde induced cell cycle arrest and cell death in BroTo and A549 cells cultured in vitro. Life Sci 73:2831–2840CrossRefPubMedGoogle Scholar
  16. Fernandes J, Da Fonseca CO, Teixeira A et al (2005) Perillyl alcohol induces apoptosis in human glioblastoma multiforme cells. Oncol Rep 13:943–947PubMedGoogle Scholar
  17. Fisher K, Phillips C (2009) The mechanism of action of a citrus oil blend against Enterococcus faecium and Enterococcus faecalis. J Appl Microbiol 106:1343–1349CrossRefPubMedGoogle Scholar
  18. Fu YJ, Chen LY, Zu YG et al (2009) The antibacterial activity of clove essential oil against Propionibacterium acnes and its mechanism of action. Arch Dermatol 145:86–88PubMedGoogle Scholar
  19. Greay SJ, Ireland DJ, Kissick HT et al (2010a) Inhibition of established subcutaneous murine tumour growth with topical Melaleuca alternifolia (tea tree) oil. Cancer Chemother Pharmacol 66:1095–1102CrossRefPubMedGoogle Scholar
  20. Greay SJ, Ireland DJ, Kissick HT et al (2010b) Induction of necrosis and cell cycle arrest in murine cancer cell lines by Melaleuca alternifolia (tea tree) oil and terpinen-4-ol. Cancer Chemother Pharmacol 65:877–888CrossRefPubMedGoogle Scholar
  21. Hammer KA, Carson CF (2011) Antibacterial and antifungal activities of essential oils. In: Thormar H (ed) Lipids and essential oils as antimicrobial agents. Wiley, West SussexGoogle Scholar
  22. Hammer KA, Carson CF, Riley TV (2008) Frequencies of resistance to Melaleuca alternifolia (tea tree) oil and rifampicin in Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis. Int J Antimicrob Agents 32:170–173CrossRefPubMedGoogle Scholar
  23. Inoue Y, Shiraishi A, Hada T et al (2004) The antibacterial effects of terpene alcohols on Staphylococcus aureus and their mode of action. FEMS Microbiol Lett 237:325–331PubMedGoogle Scholar
  24. Lambert RJW, Skandamis PN, Coote PJ et al (2001) A study of the minimum inhibitory concentration and mode of action of oregano essential oil, thymol and carvacrol. J Appl Microbiol 91:453–462CrossRefPubMedGoogle Scholar
  25. Li L, Shukla S, Lee A et al (2010) The skin cancer chemotherapeutic agent ingenol-3-angelate (PEP005) is a substrate for the epidermal multidrug transporter (ABCB1) and targets tumor vasculature. Cancer Res 70:4509–4519CrossRefPubMedCentralPubMedGoogle Scholar
  26. Ogbourne SM, Suhrbier A, Jones B et al (2004) Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death. Cancer Res 64:2833–2839CrossRefPubMedGoogle Scholar
  27. Oussalah M, Caillet S, Lacroix M (2006) Mechanism of action of Spanish oregano, Chinese cinnamon, and savory essential oils against cell membranes and walls of Escherichia coli O157:H7 and Listeria monocytogenes. J Food Prot 69:1046–1055PubMedGoogle Scholar
  28. Papadopoulos CJ, Carson CF, Chang BJ et al (2008) Role of the MexAB-OprM efflux pump of Pseudomonas aeruginosa in tolerance to tea tree (Melaleuca alternifolia) oil and its monoterpene components terpinen-4-ol, 1, 8-cineole, and alpha-terpineol. Appl Environ Microbiol 74:1932–1935CrossRefPubMedCentralPubMedGoogle Scholar
  29. Paparella A, Taccogna L, Aguzzi I et al (2008) Flow cytometric assessment of the antimicrobial activity of essential oils against Listeria monocytogenes. Food Control 19:1174–1182CrossRefGoogle Scholar
  30. Qiu J, Feng H, Lu J et al (2010) Eugenol reduces the expression of virulence-related exoproteins in Staphylococcus aureus. Appl Environ Microbiol 76:5846–5851CrossRefPubMedCentralPubMedGoogle Scholar
  31. Siller G, Gebauer K, Welburn P et al (2009) PEP005 (ingenol mebutate) gel, a novel agent for the treatment of actinic keratosis: results of a randomized, double-blind, vehicle-controlled, multicentre, phase IIa study. Australas J Dermatol 50:16–22CrossRefPubMedGoogle Scholar
  32. Stratton SP, Alberts DS, Einspahr JG et al (2010) A phase 2a study of topical perillyl alcohol cream for chemoprevention of skin cancer. Cancer Prev Res (Phila) 3:160–169CrossRefGoogle Scholar
  33. Wiseman DA, Werner SR, Crowell PL (2007) Cell cycle arrest by the isoprenoids perillyl alcohol, geraniol, and farnesol is mediated by p21(Cip1) and p27(Kip1) in human pancreatic adenocarcinoma cells. J Pharmacol Exp Ther 320:1163–1170CrossRefPubMedGoogle Scholar
  34. Xu J, Zhou F, Ji BP et al (2008) The antibacterial mechanism of carvacrol and thymol against Escherichia coli. Lett Appl Microbiol 47:174–179CrossRefPubMedGoogle Scholar
  35. Yeruva L, Pierre KJ, Elegbede A et al (2007) Perillyl alcohol and perillic acid induced cell cycle arrest and apoptosis in non small cell lung cancer cells. Cancer Lett 257:216–226CrossRefPubMedGoogle Scholar
  36. Yeruva L, Hall C, Elegbede JA et al (2010) Perillyl alcohol and methyl jasmonate sensitize cancer cells to cisplatin. Anticancer Drugs 21:1–9CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Discipline of Microbiology and Immunology (M502), School of Biomedical, Biomolecular and Chemical SciencesThe University of Western AustraliaCrawleyAustralia

Personalised recommendations